Chronic Obstructive Pulmonary Disease: Cardiovascular Effects: In clinical studies with ADVAIR DISKUS in patients with COPD, 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 patients (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 patients had a prolonged QTc interval at baseline.

In a 24-week study, 130 patients with COPD 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).

In 24-week clinical studies in patients with COPD, 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 patients).

No significant differences with salmeterol 50 mcg alone or in combination with fluticasone propionate as ADVAIR DISKUS 500/50 were 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.

HPA Axis Effects: 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.

After 36 weeks of dosing, serum cortisol concentrations in a subset of patients with COPD (n = 83) were 22% lower in patients receiving ADVAIR DISKUS 500/50 and 21% lower in patients receiving fluticasone propionate 500 mcg than in patients receiving placebo.

Other Fluticasone Propionate Products: Asthma: HPA Axis Effects: 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.

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