General Information

Serevent Diskus (salmeterol xinafoate inhalation powder) is a long-acting beta2-adrenergic agonist.

Serevent Diskus is approved for the treatment of asthma in patients aged 4 years and older with the use of an inhaled corticosteroid (ICS), the prevention of exercise-induced bronchospasm (EIB) in patients aged 4 years and older and the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease.

Serevent Diskus is for oral inhalation only.

• Treatment of asthma in patients aged 4 years and older: 1 inhalation twice daily in addition to concomitant treatment with an ICS.
• EIB: 1 inhalation at least 30 minutes before exercise.
• Maintenance treatment of bronchospasm associated with COPD: 1 inhalation twice daily

Mechanism of Action

Salmeterol is a selective LABA. In vitro studies show salmeterol to be at least 50 times more selective for beta2-adrenoceptors than albuterol. Although beta2-adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta2-agonists may have cardiac effects. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including salmeterol, 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.

Side Effects

Adverse effects associated with the use of Serevent Diskus may include:

Asthma:

• Headache
• influenza
• nasal/sinus congestion
• pharyngitis
• rhinitis
• tracheitis/bronchitis

COPD:

• Cough
• headache
• musculoskeletal pain
• throat irritation
• viral respiratory infection

Clinical Trial Results

Adult and Adolescent Subjects Aged 12 Years and Older

In 2 randomized double-blind trials, Serevent Diskus was compared with albuterol inhalation aerosol and placebo in adolescent and adult subjects with mild-to-moderate asthma (protocol defined as 50% to 80% predicted FEV1, actual mean of 67.7% at baseline), including subjects who did and who did not receive concurrent ICS. The efficacy of Serevent Diskus was demonstrated over the 12-week period with no change in effectiveness over this time period. Maintenance of efficacy for periods up to 1 year has been documented.

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 clinical trials evaluating twice-daily treatment with Serevent Diskus 50 mcg (n = 336) compared with placebo (n = 366) in subjects with chronic bronchitis with airflow limitation, with or without emphysema, improvements in pulmonary function endpoints were greater with salmeterol 50 mcg than with placebo. Treatment with Serevent Diskus did not result in significant improvements in secondary endpoints assessing COPD symptoms in either clinical trial. Both trials were randomized, double-blind, parallel-group trials of 24 weeks’ duration and were identical in design, subject entrance criteria, and overall conduct. The percent change in FEV1 refers to the change from baseline, defined as the predose value on Treatment Day 1. To account for subject withdrawals during the trial, Endpoint (last evaluable FEV1) data are provided. Subjects receiving Serevent Diskus 50 mcg had significantly greater improvements in 2-hour postdose FEV1 at Endpoint (216 mL, 20%) compared with placebo (43 mL, 5%). Improvement was apparent on the first day of treatment and maintained throughout the 24 weeks of treatment.