Short-term safety and tolerability of double-dose salmeterol/fluticasone propionate in adult asthmatic patients

The incidence of asthma exacerbations in patients receiving salmeterol/fluticasone propionate (Seretidetrade mark or Advair((R))) is low. However, when asthma control deteriorates, clinicians may instruct patients to double the dose of their inhaled corticosteroid medication for a short period. The purpose of this study was to demonstrate that doubling the dose of Seretidetrade mark for a period of 2 weeks in subjects with persistent asthma is safe and well tolerated. This randomised, double-blind, parallel-group study was conducted in primary-care centres. Adults with a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of >/=70% predicted were stratified to receive a single dose of Seretidetrade mark 50mug/100mug, 50mug/250mug or 50mug/500mug twice daily from a Diskustrade mark inhaler for a 4-week run-in period, dependent on the dose of inhaled corticosteroid on entry. Subjects were then randomised to receive either an extra inhalation of the same dose of Seretidetrade mark received during the run-in (double dose) or an inhalation of matching placebo (single dose) for 14 days in a 2 : 1 ratio. Subjects were asked to record any adverse events, morning and evening heart rate (HR), peak flow and relief medication use in daily record cards. The primary endpoint was tremor as perceived by the subject. Clinic evaluations included HR, 12-lead ECG, and potassium and glucose levels. 110 and 208 subjects received single- and double-dose Seretidetrade mark, respectively. Only one subject experienced tremor. This was classified as mild and occurred in a subject receiving double-dose Seretidetrade mark (50mug/100mug). There was no difference between the treatment groups in the incidence of tremor (difference