Salmeterol 100 μg:: an analysis of its tolerability in single- and chronic-dose studies

Background: A combination product containing fluticasone propionate 100 or 250 mug and salmeterol 50 mug has recently been made available in the United States. Some patients, if previously instructed to double their inhaled corticosteroids, may double this product, inadvertently receiving higher doses of salmeterol, potentially causing systemic beta (2)-agonist-related effects. Objectives: To examine the systemic effects of single and chronic doses of salmeterol 100 mug. Methods: Forty-four studies including a salmeterol 100 Ag treatment arm were identified. Data on predictable systemic effects were available in 10 single-dose and 9 chronic-dose studies lasting more than 7 days, in patients with asthma (6 adult, 2 pediatric) or chronic obstructive pulmonary disease (1 study), which were included in a weighted, pooled analysis. Results: Single 100-mug dose studies: mean change from baseline in heart rate was +2.3 beats per minute and systolic blood pressure +0.4 mm Hg. Tremor and palpitations were reported in 5.7% and 2.8%. Other systemic effects included a decrease in serum potassium for 3 subjects (2.1%); an increase in serum glucose, I subject (0.7%); and electrocardiographic (ECG) events, 24 cases (17.0%). Twenty-three of these were from one crossover study which reported 27 ECG events after placebo. Chronic dose studies (salmeterol 100 mug): mean change in heart rate and systolic blood pressure were +1.8 beats per minute and -0.2 mm Hg. Tremor and palpitations were reported in 5.6% and 1.7% of 1,504 patients. Thirteen recorded a decrease in serum potassium (0.9%) and 5 an increase in serum glucose (0.3%). Nine patients had ECG events (0.6%). Eight of these were "arrhythmia" from one study, which also reported 12 events before treatment. Conclusions: The mean systemic effects of salmeterol 100 mug are small and of doubtful clinical relevance. Patients (and their caregivers) can be reassured that inadvertently taking double doses of the new combination product are unlikely to affect them adversely.