Inhaled Salmeterol

Abstract

Inhaled salmeterol is a long-acting, selective β₂-adrenoceptor agonist bronchodilator. The drug has been compared with placebo, ipratropium bromide and oral theophylline in patients with chronic obstructive pulmonary disease (COPD) in randomised, clinical trials. Inhaled salmeterol 50µg twice daily produced significant improvement in forced expiratory volume in 1 second (FEV₁), equivalent to that obtained with inhaled ipratropium bromide 40µg 4 times daily and greater than that obtained with placebo or oral theophylline in randomised trials. Use of as-needed salbutamol (albuterol) was significantly reduced during treatment with inhaled salmeterol or ipratropium bromide compared with placebo or oral theophylline. The time to first COPD exacerbation was significantly longer during 12 weeks of treatment with inhaled salmeterol 50µg twice daily than ipratropium bromide 40µg 4 times daily. Compared with baseline and placebo, patients treated for 16 weeks with salmeterol 50µg (but not 100µg) twice daily reported significant improvement in total St George’s Respiratory Questionnaire (SGRQ) scores. Similarly, more patients treated with inhaled salmeterol 50µg twice daily or ipratropium bromide 40µg 4 times daily experienced an increase of ≥10 points in Chronic Respiratory Disease Questionnaire (CRQ) scores, the minimum clinically significant increment. Compared with placebo, inhaled salmeterol 50µg twice daily alone, or concurrent with ipratropium bromide 40µg 4 times daily improved lung function and reduced symptoms in patients with stable COPD in a 12-week, randomised, double-blind study. Clinically meaningful improvement in CRQ scores was documented in significantly more patients treated with the combination of the 2 drugs than either salmeterol monotherapy or placebo. Inhaled salmeterol 50µg twice daily plus oral theophylline had additive effects on lung function, increased the proportion of symptom-free days and decreased requirements for as-needed salbutamol compared with either agent alone according to a pooled analysis of 2 multicentre, randomised, double-blind studies. Conclusion: When used at the optimal dosage, 50µg twice daily, salmeterol provides symptomatic relief and improves lung function and health-related quality of life in patients with COPD. Available evidence suggests that the drug is as effective as ipratropium bromide and more effective than oral theophylline in patients with COPD. Moreover salmeterol has additive effects when used in combination with inhaled ipratropium bromide or oral theophylline. These qualities make the drug suitable for first-line use in patients with COPD who require regular bronchodilator therapy to manage symptoms. In single dose crossover studies, the long-acting selective β₂-adrenoceptor agonist salmeterol consistently produced improvements in forced expiratory volume in 1 second (FEV₁) in patients with chronic obstructive pulmonary disease (COPD) compared with baseline and placebo. There was no statistical difference in the mean peak FEV₁ after inhalation of salmeterol 50µg, formoterol 6 or 12µg, salbutamol (albuterol) 200µg, oral bambuterol 20mg, ipratropium bromide 40µg (alone or in combination with salbutamol 200µg) or oxitropium bromide 200 or 400µg. The time required to achieve peak FEV₁ tended to be somewhat longer with salmeterol than other bronchodilators, but the duration of action of a single dose of salmeterol was generally longer than other agents, with the exception of inhaled formoterol and oral bambuterol. Bronchodilation was maintained throughout ≥12 weeks of treatment with salmeterol 50µg twice daily without any evidence of tachyphylaxis. In randomised, double-blind multicentre studies, salmeterol 50µg twice daily and ipratropium bromide 40µg 4 times daily produced greater improvements in FEV₁ after 12 weeks compared with placebo. FEV₁ was >12% higher than the baseline value 12 hours after inhalation of salmeterol on both the first and last days of treatment. Significant improvements in lung function were obtained in ‘reversible’ and ‘nonreversible’ patients In patients with COPD and minimal reversibility of FEV₁ after inhaling salbutamol (≤12%), significant bronchodilation was maintained throughout 12 weeks of treatment with twice daily inhaled salmeterol 50µg administered alone or concurrently with inhaled fluticasone propionate 250 or 500µg, or oral theophylline. Use of salmeterol does not impair the response to short-acting bronchodilators in patients with COPD, as treatment for up to 12 weeks did not preclude a prompt statistically significant bronchodilator response to inhaled salbutamol or oxitropium bromide. As acute reversibility of FEV₁ after inhalation of salbutamol 200µg did not reliably predict the response to inhaled salmeterol, reversibility testing is a poor predictor of the potential response to salmeterol in patients with COPD. Compared with placebo, significant increases in FEV₁ and forced vital capacity (FVC), and decreases in functional residual capacity, residual lung volume and breathlessness scores were observed 4 hours after inhaling salmeterol 50µg. A comprehensive treatment program, which addressed the reduction in ventilatory capacity (with salmeterol), reduced ventilatory demand (through exercise training) and strengthened weakened inspiratory muscles, was effective in relieving dyspnoea in patients with COPD. Despite significant increases in FEV₁ after inhalation of single doses of inhaled β₂-adrenergic agonists, small, statistically significant and transient decreases in arterial oxygen tension, which are unlikely to be of clinical significance,...