Salmeterol 100 microg: an analysis of its tolerability in single- and chronic-dose studies.
BACKGROUND
A combination product containing fluticasone propionate 100 or 250 microg and salmeterol 50 microg 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 beta2-agonist-related effects.


OBJECTIVE
To examine the systemic effects of single and chronic doses of salmeterol 100 microg.


METHODS
Forty-four studies including a salmeterol 100 microg 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-microg 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, 1 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 microg): 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 microg 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.
Shrewsbury
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GlaxoSmithKline UK Limited, Uxbridge, Middlesex, United Kingdom. sbs40926@gsk.com
Hallett
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D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol