Drug products: Onbrez® Breezhaler®
ATC code: R03AC18
Substances: indacaterol, indacaterol maleate
More men than women have been included in the randomized controlled trials of indacaterol in chronic obstructive pulmonary disease (COPD). A large pooled analysis found that indacaterol/glycopyrronium improved lung function more than placebo and other active substances in both men and women, although improvements in health status, dyspnea, rescue medication use, and symptoms were generally larger in women than in men. A post-hoc analysis of sex differences in the annualized rates of COPD exacerbations was found to be lower in men treated with indacaterol/glycopyrronium than those treated with salmeterol/ fluticasone. There was no significant effect in women, which may be due to a low number of women included in this study. No sex differences were found regarding safety.
Indacaterol is a long-acting beta2-agonist (LABA) used for treating airflow obstruction in patients with COPD [1, 2].
Data from various studies indicate that women have increased dyspnea for a given level of airflow limitation and greater airway hyper-responsiveness, as well as greater frequency of exacerbations . Historically, more men than women had COPD and although the prevalence in most countries now is more equal trial participation has been slower to reflect this .
Cmax has been found to be 11% higher in women . A population pharmacokinetic study found smoking, age, and patient's sex to affect apparent clearance of indacaterol (5). Neither of these differences are perceived to be clinically relevant and no dose adjustment according to patient’s sex is recommended [1, 2, 4, 5].
A pooled analysis of the IGNITE program (4719 men, 1389 women) comparing the effect by sex of indacaterol/glycopyrronium on moderate to very severe COPD versus other commonly used COPD treatments and placebo found indacaterol/glycopyrronium to improve lung function more than placebo and other active comparators in both men and women (6). Improvements in health status, dyspnea, rescue medication use, and symptoms were generally larger in women than in men .
In a post-hoc analysis of sex differences in the randomized controlled FLAME trial in patients with moderate-to very severe COPD (2257 men, 805 women) the annualized rates of moderate/severe as well as all exacerbations were lower in men treated with indacaterol/glycopyrronium than those treated with salmeterol/ fluticasone . The difference was not significant in women. Time-to-first moderate/severe COPD exacerbation was lower in both indacaterol/glycopyrronium treated men and women. If this reflects the lower number of women in the study or a true difference in efficacy is not clear .
A pooled analysis of safety data from 14 randomized studies on fixed dose indacaterol/glycopyrronium, the monocomponents, or comparators in patients with COPD (in all 8 334 men, 3 064 women) found no difference in adverse events between men and women .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2019-05-28
Reviewed by: Karin Schenck-Gustafsson
Approved by: Karin Schenck-Gustafsson