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Metabolism: The total clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total. The only circulating metabolite detected in man is the 17 -carboxylic acid derivative of fluticasone propionate, which is formed through the cytochrome P450 3A4 pathway. This metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man. Elimination: Text Continues Below
Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites. Special Populations: Hepatic Impairment: Since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored. Gender: Full pharmacokinetic profiles were obtained from 9 female and 16 male patients with asthma given fluticasone propionate inhalation powder 500 mcg twice daily using the DISKUS device and from 14 female and 43 male patients with COPD given 250 or 500 mcg twice daily. No overall differences in fluticasone propionate pharmacokinetics were observed. Age: No relationship between fluticasone propionate systemic exposure and age was observed in 57 patients with COPD (aged 40 to 82 years) given 250 or 500 mcg twice daily. Other: Formal pharmacokinetic studies using fluticasone propionate have not been conducted in other special populations. Drug Interactions: Fluticasone propionate is a substrate of cytochrome P450 3A4. Coadministration of fluticasone propionate and the highly potent cytochrome P450 3A4 inhibitor ritonavir is not recommended based upon a multiple-dose, crossover drug interaction study in 18 healthy subjects. Fluticasone propionate aqueous nasal spray (200 mcg once daily) was coadministered for 7 days with ritonavir (100 mg twice daily). Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL) in most subjects, and when concentrations were detectable peak levels (Cmax averaged 11.9 pg/mL [range, 10.8 to 14.1 pg/mL] and AUC(0-) averaged 8.43 pg•hr/mL [range, 4.2 to 18.8 pg•hr/mL]). Fluticasone propionate Cmax and AUC(0-) increased to 318 pg/mL (range, 110 to 648 pg/mL) and 3,102.6 pg•hr/mL (range, 1,207.1 to 5,662.0 pg•hr/mL), respectively, after coadministration of ritonavir with fluticasone propionate aqueous nasal spray. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in plasma cortisol area under the plasma concentration versus time curve (AUC). Caution should be exercised when other potent cytochrome P450 3A4 inhibitors are coadministered with fluticasone propionate. In a drug interaction study, coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in increased plasma fluticasone propionate exposure and reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol. In another multiple-dose drug interaction study, coadministration of orally inhaled fluticasone propionate (500 mcg twice daily) and erythromycin (333 mg 3 times daily) did not affect fluticasone propionate pharmacokinetics. Salmeterol Xinafoate: Salmeterol xinafoate, an ionic salt, dissociates in solution so that the salmeterol and 1-hydroxy-2-naphthoic acid (xinafoate) moieties are absorbed, distributed, metabolized, and eliminated independently. Salmeterol acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Absorption: Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses (50 mcg of salmeterol inhalation powder twice daily). Following chronic administration of an inhaled dose of 50 mcg of salmeterol inhalation powder twice daily, salmeterol was detected in plasma within 5 to 45 minutes in 7 patients with asthma; plasma concentrations were very low, with mean peak concentrations of 167 pg/mL at 20 minutes and no accumulation with repeated doses. Distribution: The percentage of salmeterol bound to human plasma proteins averages 96% in vitro over the concentration range of 8 to 7,722 ng of salmeterol base per milliliter, much higher concentrations than those achieved following therapeutic doses of salmeterol. Metabolism: Salmeterol base is extensively metabolized by hydroxylation, with subsequent elimination predominantly in the feces. No significant amount of unchanged salmeterol base was detected in either urine or feces. Elimination: In 2 healthy subjects who received 1 mg of radiolabeled salmeterol (as salmeterol xinafoate) orally, approximately 25% and 60% of the radiolabeled salmeterol was eliminated in urine and feces, respectively, over a period of 7 days. The terminal elimination half-life was about 5.5 hours (1 volunteer only). The xinafoate moiety has no apparent pharmacologic activity. The xinafoate moiety is highly protein bound (>99%) and has a long elimination half-life of 11 days. Special Populations: Hepatic Impairment: Since salmeterol is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored. Other: Formal pharmacokinetic studies using salmeterol base have not been conducted in other special populations. Pharmacodynamics: ADVAIR DISKUS: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Four studies were conducted in healthy subjects: (1) a single-dose crossover study using 2 inhalations of ADVAIR DISKUS 500/50, fluticasone propionate powder 500 mcg and salmeterol powder 50 mcg given concurrently, or fluticasone propionate powder 500 mcg given alone, (2) a cumulative dose study using 50 to 400 mcg of salmeterol powder given alone or as ADVAIR DISKUS 500/50, (3) a repeat-dose study for 11 days using 2 inhalations twice daily of ADVAIR DISKUS 250/50, fluticasone propionate powder 250 mcg, or salmeterol powder 50 mcg, and (4) a single-dose study using 5 inhalations of ADVAIR DISKUS 100/50, fluticasone propionate powder 100 mcg alone, or placebo. In these studies no significant differences were observed in the pharmacodynamic effects of salmeterol (pulse rate, blood pressure, QTc interval, potassium, and glucose) whether the salmeterol was given as ADVAIR DISKUS, concurrently with fluticasone propionate from separate inhalers, or as salmeterol alone. The systemic pharmacodynamic effects of salmeterol were not altered by the presence of fluticasone propionate in ADVAIR DISKUS. The potential effect of salmeterol on the effects of fluticasone propionate on the hypothalamic-pituitary-adrenal (HPA) axis was also evaluated in these studies. No significant differences across treatments were observed in 24-hour urinary cortisol excretion and, where measured, 24-hour plasma cortisol AUC. The systemic pharmacodynamic effects of fluticasone propionate were not altered by the presence of salmeterol in ADVAIR DISKUS in healthy subjects. Asthma: In clinical studies with ADVAIR DISKUS in patients with asthma, no significant differences were observed in the systemic pharmacodynamic effects of salmeterol (pulse rate, blood pressure, QTc interval, potassium, and glucose) whether the salmeterol was given alone or as ADVAIR DISKUS. In 72 adolescent and adult patients with asthma given either ADVAIR DISKUS 100/50 or ADVAIR DISKUS 250/50, continuous 24-hour electrocardiographic monitoring was performed after the first dose and after 12 weeks of therapy, and no clinically significant dysrhythmias were noted. In a 28-week study in patients with asthma, ADVAIR DISKUS 500/50 twice daily was compared with the concurrent use of salmeterol powder 50 mcg plus fluticasone propionate powder 500 mcg from separate inhalers or fluticasone propionate powder 500 mcg alone. No significant differences across treatments were observed in plasma cortisol AUC after 12 weeks of dosing or in 24-hour urinary cortisol excretion after 12 and 28 weeks. In a 12-week study in patients with asthma, ADVAIR DISKUS 250/50 twice daily was compared with fluticasone propionate powder 250 mcg alone, salmeterol powder 50 mcg alone, and placebo. For most patients, the ability to increase cortisol production in response to stress, as assessed by 30-minute cosyntropin stimulation, remained intact with ADVAIR DISKUS. One patient (3%) who received ADVAIR DISKUS 250/50 had an abnormal response (peak serum cortisol <18 mcg/dL) after dosing, compared with 2 patients (6%) who received placebo, 2 patients (6%) who received fluticasone propionate 250 mcg, and no patients who received salmeterol. Chronic Obstructive Pulmonary Disease: In clinical studies with ADVAIR DISKUS in patients with COPD associated with chronic bronchitis, no significant differences were seen in pulse rate, blood pressure, potassium, and glucose between ADVAIR DISKUS, the individual components of ADVAIR DISKUS, and placebo. In a study of ADVAIR DISKUS 250/50, 8 subjects (2 [1.1%] in the group given ADVAIR DISKUS 250/50, 1 [0.5%] in the fluticasone propionate 250 mcg group, 3 [1.7%] in the salmeterol group, and 2 [1.1%] in the placebo group) had QTc intervals >470 msec at least 1 time during the treatment period. Five (5) of these 8 subjects had a prolonged QTc interval at baseline. In a 24-week study, 130 patients with COPD associated with chronic bronchitis received continuous 24-hour electrocardiographic monitoring prior to the first dose and after 4 weeks of twice-daily treatment with either ADVAIR DISKUS 500/50, fluticasone propionate powder 500 mcg, salmeterol powder 50 mcg, or placebo. No significant differences in ventricular or supraventricular arrhythmias and heart rate were observed among the groups treated with ADVAIR DISKUS 500/50, the individual components, or placebo. One (1) subject in the fluticasone propionate group experienced atrial flutter/atrial fibrillation, and 1 subject in the group given ADVAIR DISKUS 500/50 experienced heart block. There were 3 cases of nonsustained ventricular tachycardia (1 each in the placebo, salmeterol, and fluticasone propionate 500 mcg treatment groups). Short-cosyntropin stimulation testing was performed both at Day 1 and Endpoint in 101 patients with COPD receiving twice-daily ADVAIR DISKUS 250/50, fluticasone propionate powder 250 mcg, salmeterol powder 50 mcg, or placebo. For most patients, the ability to increase cortisol production in response to stress, as assessed by short cosyntropin stimulation, remained intact with ADVAIR DISKUS 250/50. One (1) patient (3%) who received ADVAIR DISKUS 250/50 had an abnormal stimulated cortisol response (peak cortisol <14.5 mcg/dL assessed by high-performance liquid chromatography) after dosing, compared with 2 patients (9%) who received fluticasone propionate 250 mcg, 2 patients (7%) who received salmeterol 50 mcg, and 1 patient (4%) who received placebo following 24 weeks of treatment or early discontinuation from study. Fluticasone Propionate: Asthma: In clinical trials with fluticasone propionate inhalation powder using doses up to and including 250 mcg twice daily, occasional abnormal short cosyntropin tests (peak serum cortisol <18 mcg/dL assessed by radioimmunoassay) were noted both in patients receiving fluticasone propionate and in patients receiving placebo. The incidence of abnormal tests at 500 mcg twice daily was greater than placebo. In a 2-year study carried out with the DISKHALER ® inhalation device in 64 patients with mild, persistent asthma (mean FEV1 91% of predicted) randomized to fluticasone propionate 500 mcg twice daily or placebo, no patient receiving fluticasone propionate had an abnormal response to 6-hour cosyntropin infusion (peak serum cortisol <18 mcg/dL). With a peak cortisol threshold of <35 mcg/dL, 1 patient receiving fluticasone propionate (4%) had an abnormal response at 1 year; repeat testing at 18 months and 2 years was normal. Another patient receiving fluticasone propionate (5%) had an abnormal response at 2 years. No patient on placebo had an abnormal response at 1 or 2 years. Chronic Obstructive Pulmonary Disease: In a 24-week study, the steady-state fluticasone propionate pharmacokinetics and serum cortisol levels were described in a subset of patients with COPD associated with chronic bronchitis (N = 86) randomized to twice-daily fluticasone propionate inhalation powder via the DISKUS 500 mcg, fluticasone propionate inhalation powder 250 mcg, or placebo. Serial serum cortisol concentrations were measured across a 12-hour dosing interval following at least 4 weeks of dosing. Serum cortisol concentrations following 250 and 500 mcg twice-daily dosing were 10% and 21% lower than placebo, indicating a dose-dependent increase in systemic exposure to fluticasone propionate. Salmeterol Xinafoate: Inhaled salmeterol, like other beta-adrenergic agonist drugs, can produce dose-related cardiovascular effects and effects on blood glucose and/or serum potassium (see PRECAUTIONS: General). The cardiovascular effects (heart rate, blood pressure) associated with salmeterol occur with similar frequency, and are of similar type and severity, as those noted following albuterol administration. Asthma: The effects of rising doses of salmeterol and standard inhaled doses of albuterol were studied in volunteers and in patients with asthma. Salmeterol doses up to 84 mcg administered as inhalation aerosol resulted in heart rate increases of 3 to 16 beats/min, about the same as albuterol dosed at 180 mcg by inhalation aerosol (4 to 10 beats/min). Adolescent and adult patients receiving 50-mcg doses of salmeterol inhalation powder (N = 60) underwent continuous electrocardiographic monitoring during two 12-hour periods after the first dose and after 1 month of therapy, and no clinically significant dysrhythmias were noted. Chronic Obstructive Pulmonary Disease: In 24-week clinical studies in patients with COPD associated with chronic bronchitis, the incidence of clinically significant electrocardiogram (ECG) abnormalities (myocardial ischemia, ventricular hypertrophy, clinically significant conduction abnormalities, clinically significant arrhythmias) was lower for patients who received salmeterol (1%, 9 of 688 patients who received either salmeterol 50 mcg or ADVAIR DISKUS) compared with placebo (3%, 10 of 370 subjects). No significant differences with salmeterol 50 mcg alone or in combination with fluticasone propionate as ADVAIR DISKUS 500/50 was observed on pulse rate and systolic and diastolic blood pressure in a subset of patients with COPD who underwent 12-hour serial vital sign measurements after the first dose (N = 183) and after 12 weeks of therapy (N = 149). Median changes from baseline in pulse rate and systolic and diastolic blood pressure were similar to those seen with placebo (see ADVERSE REACTIONS: Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis). Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown. CLINICAL TRIALS Asthma: In clinical trials comparing ADVAIR DISKUS with the individual components, improvements in most efficacy endpoints were greater with ADVAIR DISKUS than with the use of either fluticasone propionate or salmeterol alone. In addition, clinical trials showed similar results between ADVAIR DISKUS and the concurrent use of fluticasone propionate plus salmeterol at corresponding doses from separate inhalers. Studies Comparing ADVAIR DISKUS to Fluticasone Propionate Alone or Salmeterol Alone: Three (3) double-blind, parallel-group clinical trials were conducted with ADVAIR DISKUS in 1,208 adolescent and adult patients ( 12 years, baseline FEV1 63% to 72% of predicted normal) with asthma that was not optimally controlled on their current therapy. All treatments were inhalation powders, given as 1 inhalation from the DISKUS device twice daily, and other maintenance therapies were discontinued. Study 1: Clinical Trial With ADVAIR DISKUS 100/ 50: This placebo-controlled, 12-week, US study compared ADVAIR DISKUS 100/50 with its individual components, fluticasone propionate 100 mcg and salmeterol 50 mcg. The study was stratified according to baseline asthma maintenance therapy; patients were using either inhaled corticosteroids (N = 250) (daily doses of beclomethasone dipropionate 252 to 420 mcg; flunisolide 1,000 mcg; fluticasone propionate inhalation aerosol 176 mcg; or triamcinolone acetonide 600 to 1,000 mcg) or salmeterol (N = 106). Baseline FEV1 measurements were similar across treatments: ADVAIR DISKUS 100/50, 2.17 L; fluticasone propionate 100 mcg, 2.11 L; salmeterol, 2.13 L; and placebo, 2.15 L. Predefined withdrawal criteria for lack of efficacy, an indicator of worsening asthma, were utilized for this placebo-controlled study. Worsening asthma was defined as a clinically important decrease in FEV1 or peak expiratory flow (PEF), increase in use of VENTOLIN ® (albuterol, USP) Inhalation Aerosol, increase in night awakenings due to asthma, emergency intervention or hospitalization due to asthma, or requirement for asthma medication not allowed by the protocol. As shown in Table 1, statistically significantly fewer patients receiving ADVAIR DISKUS 100/50 were withdrawn due to worsening asthma compared with fluticasone propionate, salmeterol, and placebo. Table 1. Percent of Patients Withdrawn Due to Worsening Asthma in Patients Previously Treated With Either Inhaled Corticosteroids or Salmeterol (Study 1)
ADVAIR DISKUS
100/50
(N = 87) Fluticasone Propionate
100 mcg
(N = 85) Salmeterol
50 mcg
(N = 86)
Placebo
(N = 77)
3% 11% 35% 49% The FEV1 results are displayed in Figure 1. Because this trial used predetermined criteria for worsening asthma, which caused more patients in the placebo group to be withdrawn, FEV1 results at Endpoint (last available FEV1 result) are also provided. Patients receiving ADVAIR DISKUS 100/50 had significantly greater improvements in FEV1 (0.51 L, 25%) compared with fluticasone propionate 100 mcg (0.28 L, 15%), salmeterol (0.11 L, 5%), and placebo (0.01 L, 1%). These improvements in FEV1 with ADVAIR DISKUS were achieved regardless of baseline asthma maintenance therapy (inhaled corticosteroids or salmeterol). Figure 1. Mean Percent Change From Baseline in FEV1 in Patients With Asthma Previously Treated With Either Inhaled Corticosteroids or Salmeterol (Study 1)
The effect of ADVAIR DISKUS 100/50 on morning and evening PEF endpoints is shown in Table 2. Table 2. Peak Expiratory Flow Results for Patients With Asthma Previously Treated With Either Inhaled Corticosteroids or Salmeterol (Study 1) Efficacy Variable *
ADVAIR
DISKUS
100/50
(N = 87) Fluticasone
Propionate
100 mcg
(N = 85) Salmeterol
50 mcg
(N = 86)
Placebo
(N = 77)
AM PEF (L/min)
Baseline 393 374 369 382
Change from baseline 53 17 -2 -24
PM PEF (L/min)
Baseline 418 390 396 398
Change from baseline 35 18 -7 -13 *
Change from baseline = change from baseline at Endpoint (last available data). The subjective impact of asthma on patients’ perception of health was evaluated through use of an instrument called the Asthma Quality of Life Questionnaire (AQLQ) (based on a 7-point scale where 1 = maximum impairment and 7 = none). Patients receiving ADVAIR DISKUS 100/50 had clinically meaningful improvements in overall asthma-specific quality of life as defined by a difference between groups of 0.5 points in change from baseline AQLQ scores (difference in AQLQ score of 1.25 compared to placebo). Study 2: Clinical Trial With ADVAIR DISKUS 250/ 50: This placebo-controlled, 12-week, US study compared ADVAIR DISKUS 250/50 with its individual components, fluticasone propionate 250 mcg and salmeterol 50 mcg in 349 patients with asthma using inhaled corticosteroids (daily doses of beclomethasone dipropionate 462 to 672 mcg; flunisolide 1,250 to 2,000 mcg; fluticasone propionate inhalation aerosol 440 mcg; or triamcinolone acetonide 1,100 to 1,600 mcg). Baseline FEV1 measurements were similar across treatments: ADVAIR DISKUS 250/50, 2.23 L; fluticasone propionate 250 mcg, 2.12 L; salmeterol, 2.20 L; and placebo, 2.19 L. Efficacy results in this study were similar to those observed in Study 1. Patients receiving ADVAIR DISKUS 250/50 had significantly greater improvements in FEV1 (0.48 L, 23%) compared with fluticasone propionate 250 mcg (0.25 L, 13%), salmeterol (0.05 L, 4%), and placebo (decrease of
ADVAIR DISKUS 250/50 were withdrawn from this study for worsening asthma (4%) compared with fluticasone propionate (22%), salmeterol (38%), and placebo (62%). In addition, ADVAIR DISKUS 250/50 was superior to fluticasone propionate, salmeterol, and placebo for improvements in morning and evening PEF. Patients receiving ADVAIR DISKUS 250/50 also had clinically meaningful improvements in overall asthma-specific quality of life as described in Study 1 (difference in AQLQ score of 1.29 compared to placebo). Study 3: Clinical Trial With ADVAIR DISKUS 500/ 50: This 28-week, non-US study compared ADVAIR DISKUS 500/50 with fluticasone propionate 500 mcg alone and concurrent therapy (salmeterol 50 mcg plus fluticasone propionate 500 mcg administered from separate inhalers) twice daily in 503 patients with asthma using inhaled corticosteroids (daily doses of beclomethasone dipropionate 1,260 to 1,680 mcg; budesonide 1,500 to 2,000 mcg; flunisolide 1,500 to 2,000 mcg; or fluticasone propionate inhalation aerosol 660 to 880 mcg [750 to 1,000 mcg inhalation powder]). The primary efficacy parameter, morning PEF, was collected daily for the first 12 weeks of the study. The primary purpose of weeks 13 to 28 was to collect safety data. Baseline PEF measurements were similar across treatments: ADVAIR DISKUS 500/50, 359 L/min; fluticasone propionate 500 mcg, 351 L/min; and concurrent therapy, 345 L/min. As shown in Figure 2, morning PEF improved significantly with ADVAIR DISKUS 500/50 compared with fluticasone propionate 500 mcg over the 12-week treatment period.
Improvements in morning PEF observed with ADVAIR DISKUS 500/50 were similar to improvements observed with concurrent therapy. Figure 2. Mean Percent Change From Baseline in Morning Peak Expiratory Flow in Patients With Asthma Previously Treated With Inhaled Corticosteroids (Study 3) Onset of Action and Progression of Improvement in Asthma Control: The onset of action and progression of improvement in asthma control were evaluated in the 2 placebo-controlled US trials. Following the first dose, the median time to onset of clinically significant bronchodilatation ( 15% improvement in FEV1) in most patients was seen within 30 to 60 minutes. Maximum improvement in FEV1 generally occurred within 3 hours, and clinically significant improvement was maintained for 12 hours (see Figure 3). Following the initial dose, predose FEV1 relative to Day 1 baseline improved markedly over the first week of treatment and continued to improve over the 12 weeks of treatment in both studies.
No diminution in the 12-hour bronchodilator effect was observed with either ADVAIR DISKUS 100/50 (Figures 3 and 4) or ADVAIR DISKUS 250/50 as assessed by FEV1 following 12 weeks of therapy. Figure 3. Percent Change in Serial 12-hour FEV1
in Patients With Asthma Previously Using Either Inhaled Corticosteroids or Salmeterol (Study 1) First Treatment Day Figure 4. Percent Change in Serial 12-hour FEV1
in Patients Previously With Asthma Using Either Inhaled Corticosteroids or Salmeterol (Study 1) Last Treatment Day (Week 12) Reduction in asthma symptoms, use of rescue VENTOLIN Inhalation Aerosol, and improvement in morning and evening PEF also occurred within the first day of treatment with ADVAIR DISKUS, and continued to improve over the 12 weeks of therapy in both studies. Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis: In a clinical trial evaluating twice-daily treatment with ADVAIR DISKUS 250/50 in patients with COPD associated with chronic bronchitis, improvements in lung function (as defined by predose and postdose FEV1) were significantly greater with ADVAIR DISKUS than with fluticasone propionate 250 mcg, salmeterol 50 mcg, or placebo. The study was a randomized, double-blind, parallel-group, 24-week trial. All patients had a history of cough productive of sputum that was not attributable to another disease process on most days for at least 3 months of the year for at
least 2 years. Study treatments were inhalation powders given as 1 inhalation from the DISKUS device twice daily. Maintenance COPD therapies were discontinued, with the exception of theophylline. Figures 5 and 6 display predose and 2-hour postdose FEV1 results. To account for patient withdrawals during the study, FEV1 at Endpoint (last evaluable FEV1) was evaluated. Patients receiving ADVAIR DISKUS 250/50 had significantly greater improvements in predose FEV1 at Endpoint (165 mL, 17%) compared with salmeterol 50 mcg (91 mL, 9%) and placebo (1 mL, 1%), demonstrating the contribution of fluticasone propionate to the improvement in lung function with ADVAIR DISKUS (Figure 5). Patients receiving ADVAIR DISKUS 250/50 had significantly greater improvements in postdose FEV1 at Endpoint (281 mL, 27%) compared with fluticasone propionate 250 mcg (147 mL, 14%) and placebo (58 mL, 6%), demonstrating the contribution of salmeterol to the improvement in lung function with ADVAIR DISKUS
(Figure 6).
A similar degree of improvement in lung function was also observed with ADVAIR DISKUS
500/50 twice daily. Figure 5. Predose FEV1: Mean Percent Change From Baseline in Patients With COPD Associated With Chronic Bronchitis Figure 6. Two-Hour Postdose FEV1: Mean Percent Changes From Baseline
Over Time in Patients With COPD Associated With Chronic Bronchitis Patients treated with ADVAIR DISKUS 250/50 or ADVAIR DISKUS 500/50 did not have a significant reduction in chronic bronchitis symptoms (as measured by the Chronic Bronchitis Symptom Questionnaire) or in COPD exacerbations compared to patients treated with placebo over the 24 weeks of therapy. The improvement in lung function with ADVAIR DISKUS 500/50 was similar to the improvement seen with ADVAIR DISKUS 250/50. Since there is evidence of more systemic exposure to fluticasone propionate from this higher dose and no documented advantage for efficacy, ADVAIR DISKUS 500/50 is not recommended for use in COPD. The benefit of treatment of patients with COPD associated with chronic bronchitis with ADVAIR DISKUS 250/50 for periods longer than 6 months has not been evaluated. Page: << Prev | 1 | 2 | 3 | 4 | 5
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