Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma

This double-blind, double-dummy, crossover study evaluated the tolerability of high-dose formoterol and salbutamol. Sixteen adults with mild/moderate persistent asthma (FEV1≥70% predicted) were randomized to receive either formoterol 36 μg three times daily (TID) at 5-h intervals via Aerolizer® (total daily dose 108 μg), or salbutamol 600 μg TID via pressurized metered-dose inhaler (total daily dose 1800 μg) for 3 consecutive days. After a 3-7-day washout period patients received the other treatment. FEV1 was measured 15 min pre-dose and 2 h post-dose. Both formoterol and salbutamol were associated with decreased plasma potassium (mean of minimum values: 3.4 and 3.6 mmol/L, respectively; P<0.001), increased serum glucose (mean of maximum values: 8.3 and 7.9 mmol/L, respectively; P=0.021), and small increases in mean QTc interval (mean of maximum values: 428.8 and 417.4 ms, respectively; P<0.001). However, none of these effects was clinically significant. Both treatments increased FEV1 to a mean maximum of 4.6 L (P=0.613), but the mean FEV1 AUC0-72 h for formoterol was significantly greater than for salbutamol (302.2 L h, vs. 277.4 L h; P<0.001). No patients discontinued due to treatment-related adverse events. High-dose formoterol via Aerolizer® did not produce any clinically significant systemic effects in patients with mild/moderate asthma.