Indications for: SEREVENT DISKUS
As an adjunct to inhaled corticosteroid (ICS) for the treatment of asthma and in the prevention of bronchospasm in reversible obstructive airway disease (including nocturnal asthma). Prevention of exercise-induced bronchospasm (EIB). Maintenance treatment of COPD-associated bronchospasm in adults.
Limitations of Use:
Not for relief of acute bronchospasm.
Asthma: Adult and Adolescent Subjects Aged 12 Years and Older
In 2 randomized, double-blind trials, the efficacy of Serevent Diskus was compared with albuterol inhalation aerosol and placebo in adolescent and adult patients with mild to moderate asthma (protocol defined as 50% to 80% predicted FEV1, actual mean of 67.7% at baseline), including those with or without conconcurrent ICS.
In the combined data for both trials, there was no change in effectiveness of Serevent Diskus and no gender- or age-related differences in safety or efficacy after the 12-week period. Moreover, treatment with Serevent Diskus had a change in the mean AM peak expiratory flow of +32 L/min at week 12 from baseline compared with no change for albuterol inhalation aerosol and +2 L/min for placebo (both P <.001). The change in the mean percentage of nights with no awakenings at week 12 from baseline was +22% for the Serevent Diskus arm compared with +3% for albuterol inhalation aerosol and +3% for placebo (both P <.001). The Serevent Diskus treatment arm had a mean reduction of -2.7 inhalations per day for rescue medications at week 12 from baseline compared with -0.9 inhalations for placebo (P <.001).
Subjects on Concomitant Inhaled Corticosteroids:
In 4 clinical trials in adult and adolescent subjects with asthma (N = 1922), the effect of adding Serevent Inhalation Aerosol to ICS therapy was evaluated over a 24-week treatment period. The trials compared the addition of salmeterol therapy to an increase (at least doubling) of the ICS dose.
In 2 randomized, double-blind, controlled, parallel-group clinical trials, 997 patients 18 to 82 years of age were enrolled with persistent asthma who were previously maintained but not on adequately controlled on ICS therapy. All patients were switched to beclomethasone dipropionate (BDP) 168 mcg twice daily during a 2-week run-in period. If patients were still not adequately controlled, then they were randomly assigned to receive either the addition of Serevent Inhalation Aerosol 42 mcg twice daily or an increase of BDP to 336 mcg twice daily.
Both the doubling dose of BDP and the addition of Serevent Inhalation Aerosol achieved statistically significantly greater improvements in pulmonary function and asthma symptoms, and statistically significantly greater reduction in supplemental albuterol use. There was no difference between the two treatment arms for the percentage of patients who experienced asthma exacerbations.
Additionally, in 2 randomized, double-blind, controlled, parallel-group clinical trials, 925 patients 12 to 78 years of age were enrolled with persistent asthma who were previously maintained but not adequately controlled on prior asthma therapy. All patients were switched to fluticasone propionate 88 mcg twice daily during the 2- to 4-week run-in period. If patients were still not adequately controlled, then they were randomly assigned to receive either the addition of Serevent Inhalation Aerosol 42 mcg twice daily or an increase of fluticasone propionate to 220 mcg twice daily.
Both the increased dose of fluticasone propionate and the addition of Serevent Inhalation Aerosol achieved statistically significantly greater improvements in pulmonary function and asthma symptoms, and statistically significnatly greater reductions in supplement albuterol use. There were fewer patients treated with Serevent Inhalation Aerosol who experienced asthma exacerbations compared with the higher dose of fluticasone propionate.
In a randomized, double-blind, controlled trial, the efficacy of Serevent Diskus was evaluated in 449 pediatric patients with asthma who did and who did not receive concurrent ICS. Over the 12-week treatment period, results showed that treatment with Serevent Diskus 50 mcg achieved a periodic serial PEF (36% to 39% postdose increase from baseline) and FEV1 (32% to 33% postdose increase from baseline). Salmeterol was effective in demographic subgroup analyses (gender and age) and was effective when coadministered with other inhaled asthma medications such as short-acting bronchodilators and ICS.
Salmeterol Multicenter Asthma Research Trial
The randomized, double-blind SMART trial evaluated the safety of salmeterol (Serevent Inhalation Aerosol) in LABA-naive patients with asthma (average age of 39 years; 71% Caucasian, 18% African American, 8% Hispanic). Patients were randomly assigned to receive salmeterol (Serevent Inhalation Aerosol) 42 mcg twice daily or placebo when added to usual asthma therapy over 28 weeks.
In an interim analysis, patients receiving salmeterol had an increased risk for fatal asthma events. In the total population, there was a higher rate of asthma-related death in patients treated with salmeterol compared with those treated with placebo (0.10% vs 0.02%, relative risk: 4.37 [95% CI, 1.25-15.34]).
Post hoc subpopulation analyses:
In Caucasians, there was a higher rate of asthma-related death that occurred in patients treated with salmeterol compared with those treated with placebo (0.07% vs 0.01%, relative risk: 5.82 [95% CI, 0.70-48.37]).
In African Americans, there was also a higher rate of asthma-related death that occurred in patients treated with salmeterol compared with those treated with placebo (0.31% vs 0.04%, relative risk: 7.26 [95% CI, 0.89-58.94]). The estimate of excess deaths in patients treated with salmeterol was greater in African Americans.
In pediatric subjects aged 12 to 18 years, respiratory-related death or life-threatening experience occurred at a similar rate in the salmeterol and the placebo groups. All-cause hospitalization, however, was increased in the salmeterol group (2% [35/1653]) versus the placebo group (less than 1% [16/162]).
Exercise-Induced Bronchospasm (EIB)
In 2 randomized, single-dose, crossover trials in adolescents and adults with EIB (N = 52), 50 mcg of Serevent Diskus prevented EIB when dosed 30 minutes prior to exercise. For some subjects, this protective effect against EIB was still apparent up to 8.5 hours following a single dose.
In 2 randomized trials in children aged 4 to 11 years with asthma and EIB (N = 50), a single 50-mcg dose of Serevent Diskus prevented EIB when dosed 30 minutes prior to exercise, with protection lasting up to 11.5 hours in repeat testing following this single dose in many subjects.
Chronic Obstructive Pulmonary Disease
In 2 randomized, double-blind, parallel-group clinical trials, the efficacy of Serevent Diskus was evaluated in patients with chronic bronchitis with airflow limitation, with or without emphysema, for 24 weeks. Patients received either Serevent Diskus 50 mcg twice daily (n=336) or placebo (n=366).
Results showed that treatment with Serevent Diskus achieved greater improvements in pulmonary function endpoints compared with placebo. There were significantly greater improvements in 2-hour postdose FEV1 at Endpoint (216 mL, 20%) compared with placebo (43 mL, 5%). Improvement was observed on the first day of treatment and maintained throughout the 24 weeks of treatment. In both trials, the Serevent Diskus group did not achieve significant improvements in secondary endpoints for COPD symptoms.
Onset of Action and Duration of Effect:
In a subset of 87 patients, the onset of action and duration of effect of Serevent Diskus was evaluated.
At 2 hours following the first 50 mcg dose, there was significant improvement in pulmonary function observed, which was the mean FEV1 increase of 12% or more and at least 200 mL.
The mean time to peak bronchodilator effect was 4.75 hours. The evidence of bronchodilatation was observed throughout the 12-hour period, and the bronchodilating effect was observed after 12 weeks of treatment similar to that seen after the first dose.
After 12 weeks of treatment, the mean time to peak bronchodilator effect was 3.27 hours.
Adults and Children:
Allow approx. 12hrs between doses. Asthma: ≥4yrs: 1 inh twice daily with concomitant ICS. EIB: ≥4yrs: 1 inh at least 30mins before exercise; do not use additional doses for 12hrs after administration or if already using twice daily dosing. COPD: 1 inh twice daily. Max 1 inh twice daily.
SEREVENT DISKUS Contraindications:
Treatment of asthma without concomitant use of ICS. Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures. Severe hypersensitivity to milk protein.
SEREVENT DISKUS Warnings/Precautions:
LABA monotherapy (without ICS) may increase risk of asthma-related events (death, hospitalizations, intubations). Do not use for asthma adequately controlled on low- or medium-dose ICS. Use fixed-dose combination product of an ICS and a LABA in children with asthma to ensure adherence. Do not initiate in rapidly or acutely deteriorating asthma or COPD. Salmeterol is not a substitute for steroids. Not for use with other long-acting β2-agonists. Do not exceed recommended dose. Prescribe a short-acting, inhaled β2-agonist for acute symptoms; monitor for increased need. Discontinue if paradoxical bronchospasm occurs; use alternative therapy. Cardiovascular disease (esp. coronary insufficiency, arrhythmias, hypertension). Convulsive disorders. Thyrotoxicosis. Hyperresponsiveness to sympathomimetics. Diabetes. Ketoacidosis. Hypokalemia. Hyperglycemia. Hepatic impairment; monitor. Labor & delivery. Pregnancy. Nursing mothers.
SEREVENT DISKUS Classification:
Long-acting beta-2 agonist (LABA).
SEREVENT DISKUS Interactions:
Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, atazanavir, clarithromycin, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin): not recommended. Caution during or within 2 weeks of discontinuing MAOIs or tricyclic antidepressants, β-blockers (consider cardioselective), K+-depleting diuretics.
Headache, influenza, nasal/sinus congestion, pharyngitis, rhinitis, tracheitis/bronchitis, cough, musculoskeletal pain, throat irritation, viral respiratory infection.
In 2 healthy adult 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 has a long elimination half-life of 11 days.
Diskus (60 blisters)—1