No serious adverse events occurred during this study and no patient required hospitalization for worsening of asthma. Adverse events occurred in 24 percent to 34 percent of patients (Table 5). Headache, the most common adverse event, was reported at similar rates within each treatment group. Tremor, the only statistically significant adverse event, was reported on five occasions by patients receiving the 84-fig dose of salmeterol.
Small but statistically significant increases (up to 8 beats/min) in resting pulse rates were found in patients who received the 84-/*g dose of salmeterol at treatment day 1 (p<0.02) compared with those in the placebo group. Compared with placebo, salmeterol did not produce any clinically significant changes in systolic or diastolic blood pressures or respiratory rates. There were no clinically significant changes in laboratory values during the study.
This study demonstrated that doses of salmeterol ranging from 10.5 fig to 84 fig produced a clear initial dose response in both magnitude and duration of bronchodilation. After 1 week of treatment, the separation of dose-dependent effects was still present for several clinical parameters but was less obvious. Over the course of the study, consistent 12-h effectiveness occurred only in patients treated with salmeterol, 42 fig or 84 fig. Canadian family pharmacy itat on The results of this 1-week study confirm and extend those of an earlier study of single inhaled doses of salmeterol, ranging from 12.5 fig to 100 fig. In that study, salmeterol was shown to have substantial and long-lasting bronchodilator activity, and on the basis of the efficacy and side effect data, the authors indicated that the 50-fig dose (actuated dose equals 42 fig) was most appropriate for patients with moderate asthma. The present study did not detect large differences in efficacy between the 21-^g and 42-/xg doses of salmeterol or between the 42-/xg and 84-fig doses. This is not surprising in that studies with relatively small numbers of patients and limited treatment duration often will not yield statistically significant differences between individual treatments. Although a dose-dependent effect of salmeterol was observed, the increased frequency of pharmacologically predictable adverse events (ie, tremor) in patients who received the 84-fig dose leads to the same recommendation made by the authors of the dose-re-sponse study mentioned above, that is, salmeterol, 42 fig every 12 h, should be considered the optimal dosage regimen for patients with mild-to-moderate asthma.
Improvement seen in morning PEF in this study and the decreased frequency of nocturnal awakenings due to asthma suggest that salmeterol is effective in controlling nocturnal asthma. One long-term study has demonstrated that salmeterol, 42 fig twice daily, can decrease by more than half the number of nights with awakenings due to asthma symptoms, while a sleep laboratory study showed that salmeterol (50 fig) improves objective sleep quality in patients with nocturnal asthma.
In summary, our data show that compared with placebo, all doses of salmeterol significantly increased FEVi and PEF, reduced the requirement for back-up albuterol, and decreased symptoms of asthma. A dose-dependent effect of salmeterol was evident, but because of the higher incidence of adverse events in the 84-fig group, we conclude that salmeterol, 42 fig twice daily, is the optimal dosage regimen for patients with mild-to-moderate asthma who require an inhaled bronchodilator for control of asthma symptoms.
Table 5—Adverse Events Reported During Study
|Type of Event||No. of Events by Treatment (n=No. of Patients)|
|No. of patients with||10||7||11||8||10|
|one or more event (%)||(29)||(24)||(34)||(24)||(32)|