Drug products: Bevespi Aerosphere, Enerzair Breezhaler, Seebri Breezhaler, Trimbow, Trixeo Aerosphere, Ultibro Breezhaler
ATC code: R03AL04, R03AL07, R03AL09, R03AL11, R03AL12, R03BB06
Substances: glycopyrronium, glycopyrronium bromide
The patient’s sex has no apparent influence on systemic exposure of glycopyrronium and no dosing adjustment is therefore necessary based on sex. The data are inconclusive concerning treatment effects and adverse effects. In general, the studies have included more men than women and significant differences between the sexes in baseline characteristics existed.
COPD (chronic obstructive pulmonary disease) affects more women than men and women often get a more serious and rapidly progressive disease . Adult asthma is more common in women while childhood asthma is more common in boys. The reversal of this sex difference in prevalence occurs around puberty which suggests that sex hormones may play a role in the etiology of asthma . However, some studies suggest that there are sex differences in expression and diagnosing of asthma, and it has been discussed if women are under-treated for respiratory diseases or not [3, 4].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 .
There were no sex-differences in the systemic exposure of glycopyrronium . Therefore, pharmacokinetic parameters of glycopyrronium showed that no dosing adjustment was necessary based on the patient´s sex . Neither did the patient´s sex affect the pharmacokinetics of the fixed dose combination indacaterol/glycopyrronium bromide in a clinically relevant way in another study .
A pooled analysis of the IGNITE program (4719 men, 1389 women) comparing sex differences 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. Improvements in health status, dyspnea, rescue medication use, and symptoms were generally larger in women than in men .
The treatment effects of the fixed combination of indacaterol maleate and glycopyrronium bromide were consistent irrespective of the patient´s sex . However, in a post hoc analysis of pooled data from two randomized, double-blind, placebo-controlled studies (724 men, 569 women), treatment with nebulized glycopyrronium 50 mcg, significantly decreased the risk of clinically important deterioration of COPD symptoms in men but not in women .
In clinical trials of the fixed combination of indacaterol and glycopyrronium bromide, female patients, in both active and placebo groups, reported more adverse events than male patients. This is a known phenomenon in clinical trials. Thus, it is difficult to determine if and to what extent glycopyrronium bromide influenced the differences in reported adverse events between the sexes .
A pooled analysis of safety data from 14 randomized studies on fixed dose indacaterol/glycopyrronium, the monocomponents, or comparators in patients with COPD (in total 8 334 men, 3 064 women) found no difference in adverse events between men and women .
No evidence is found that patient's sex affects the risk of adverse event in studies using other formulations of glycopyrronium apart from oral solutions, as well as the pharmacokinetic study conducted with Sialanar .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
In many studies there were significant differences between the sexes regarding baseline characteristics [9, 13]. In a pooled analysis (4719 men, 1389 women), comparing the effect of indacaterol/glycopyrronoium by sex versus other commonly used COPD treatments and placebo, sex differences were observed in several baseline characteristics. Women were younger, had a higher BMI and more likely to be current smokers albeit having a shorter smoking history . A post-hoc analysis (2557 men, 805 women) compared treatment response to indacaterol/glycopyrronium versus, salmeterol/fluticasone in COPD patients. Women at baseline were younger, more often current smokers and had poorer health status. Women also experienced exacerbations more frequently despite having better lung function and were treated more often with inhaled corticosteroids than men .
Date of litterature search: 2020-12-29
Reviewed by: Diana Rydberg
Approved by: Karin Schenck-Gustafsson