Salmeterol Xinafoate

LABA, including salmeterol, the active ingredient in SEREVENT DISKUS, increase the risk of asthma-related death. Data from a large 28-week placebo-controlled US trial that compared the safety of salmeterol or placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients [see WARNINGS AND PRECAUTIONS, Clinical Studies].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience In Asthma

Two multicenter, 12-week, placebo-controlled clinical trials evaluated twice-daily doses of SEREVENT DISKUS in subjects aged 12 years and older with asthma. Table 1 reports the incidence of adverse reactions in these 2 trials.

Table 1: Adverse Reactions With SEREVENT DISKUS With ≥ 3 Incidence and More Common Than Placebo in Adult and Adolescent Subjects With Asthma

Table 1 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of ≥ 3% in the group treated with SEREVENT DISKUS and were more common than in the placebo group.

Pharyngitis, sinusitis, upper respiratory tract infection, and cough occurred at ≥ 3% but were more common in the placebo group. However, throat irritation has been described at rates exceeding that of placebo in other controlled clinical trials.

Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with asthma treated with SEREVENT DISKUS compared with subjects treated with placebo include the following: contact dermatitis, eczema, localized aches and pains, nausea, oral mucosal abnormality, pain in joint, paresthesia, pyrexia of unknown origin, sinus headache, and sleep disturbance.

Two multicenter, 12-week, controlled trials have evaluated twice-daily doses of SEREVENT DISKUS in subjects aged 4 to 11 years with asthma. Table 2 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of 3% or greater in the group receiving SEREVENT DISKUS and were more common than in the placebo group.

Table 2: Adverse Reaction Incidence in Two 12-Week Pediatric Clinical Trials in Subjects With Asthma

The following events were reported at an incidence of greater than 1% in the salmeterol group and with a higher incidence than in the albuterol and placebo groups: gastrointestinal signs and symptoms, lower respiratory signs and symptoms, photodermatitis, and arthralgia and articular rheumatism.

In clinical trials evaluating concurrent therapy of salmeterol with inhaled corticosteroids, adverse events were consistent with those previously reported for salmeterol, or with events that would be expected with the use of inhaled corticosteroids.

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.

Clinical Trials Experience In Chronic Obstructive Pulmonary Disease

Two multicenter, 24-week, placebo-controlled US trials evaluated twice-daily doses of SEREVENT DISKUS in subjects with COPD. For presentation (Table 3), the placebo data from a third trial, identical in design, subject entrance criteria, and overall conduct but comparing fluticasone propionate with placebo, were integrated with the placebo data from these 2 trials (total N = 341 for salmeterol and 576 for placebo).

Table 3: Adverse Reactions With SEREVENT DISKUS With ≥ 3% Incidence in US Controlled Clinical Trials in Subjeci ts With Chronic Obstructive Pulmonary Diseasea

Other adverse reactions occurring in the group receiving SEREVENT DISKUS that occurred at a frequency of ≥ 1% and were more common than in the placebo group were as follows: anxiety; arthralgia and articular rheumatism; bone and skeletal pain; candidiasis mouth/throat; dental discomfort and pain; dyspeptic symptoms; edema and swelling; gastrointestinal infections; hyperglycemia; hyposalivation; keratitis and conjunctivitis; lower respiratory signs and symptoms; migraines; muscle pain; muscle stiffness, tightness, and rigidity; musculoskeletal inflammation; pain; and skin rashes.

Adverse reactions to salmeterol are similar in nature to those seen with other selective beta2-adrenoceptor agonists, e.g., tachycardia; palpitations; immediate hypersensitivity reactions, including urticaria, angioedema, rash, bronchospasm; headache; tremor; nervousness; and paradoxical bronchospasm.

There were no clinically relevant changes in these trials. Specifically, no changes in potassium were noted.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of salmeterol. 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 salmeterol or a combination of these factors.

In extensive US and worldwide postmarketing experience with salmeterol, serious exacerbations of asthma, including some that have been fatal, have been reported. In most cases, these have occurred in patients with severe asthma and/or in some patients in whom asthma has been acutely deteriorating [see WARNINGS AND PRECAUTIONS], but they have also occurred in a few patients with less severe asthma. It was not possible from these reports to determine whether salmeterol contributed to these events.

Arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) and anaphylaxis.

Very rare anaphylactic reaction in patients with severe milk protein allergy.

Reports of upper airway symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking; oropharyngeal irritation.

Included as part of the PRECAUTIONS section.