Drug products: Aerivio Spiromax, Airflusal Forspiro, Atemur Diskus, Brisomax Diskus, Brisomax Diskus forte, Flixotide Diskus, Flixotide Evohaler, Flixotide Evohaler 250 micrograms, Flixotide® Diskus®, Fluticasone Cipla, Flutide Diskus, Flutide Evohaler, Flutide® Diskus®, Flutide® Evohaler®, Flutiform, Flutiform K-haler, Icsori, Relanio, Salflumix Easyhaler, Salmeterol/Fluticasone Cipla, Salmeterol/Flutikason 2care4, Salmeterol/Flutikason Ebb, Salmex, Seretaide Diskus, Seretide Diskus, Seretide Diskus forte, Seretide Diskus mite, Seretide Diskus Mite, Seretide Evohaler, Seretide Evohaler forte, Seretide® Diskus®, Seretide® Diskus® forte, Seretide® Diskus® mite, Seretide® Evohaler®, Seretide® Evohaler® forte, Seretide® Evohaler® mite, Veraspir Diskus
ATC code: R03AK06, R03AK11, R03BA05
There are some studies with analyses of sex differences in effect and safety of fluticasone but the results are contradictory and the clinical relevance is unclear.
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.
Both men and women have been included in most of the pharmacokinetic studies of fluticasone. However, no analysis of sex differences have been found and sex-divided data is lacking .
Difference between men and women in effects in the efficacy of fluticasone has been investigated in a post-hoc analysis of a large 1-year double-blind trial, TRISTAN where Chronic Obstructive Pulmonary Disease (COPD) patients (539 men, 180 women) were randomized to the salmeterol/fluticasone or placebo [6,7]. No differences between men and women was found for any study outcome; FEV improvement, a reduction in COPD exacerbation rate, a reduction in COPD exacerbation requiring treatment with oral corticosteroids and improvement in health status.
The effect of fluticasone on airway responsiveness was investigated in a small 6 weeks randomized placebo-controlled study (10 men, 16 women in the fluticasone group) . The multiple linear regression analysis found a greater effect of fluticasone in men than women (3.2 vs. 1.2 doublings, respectively, of the PD20 geometric mean). However, these findings may reflect the differences in airway responsiveness in general between men and women. The excess of bronchial hyperresponsiveness in women has also been reported .
A post hoc-analysis to The TORCH study, a trial investigated the effect of fluticasone and/or salmeterol therapy (4631 men, 1481 women) over 3 years showed that women were 16% less likely to die over the period of the study compared to men . However, correcting for important covariates, such as degree of airflow obstruction, body mass index, region of the world, and previous myocardial infarction, this difference was not statistically significant (HR 1.16). The causes of death were similar in men and women .
The ISOLDE study was a trial that randomized 752 patients with moderate to severe COPD to fluticasone or placebo for three years . In a longer follow-up of >13 years of the subjects with moderate to severe COPD (280 men, 95 women), male sex was one of the factors, associated with higher mortality among other factors such as older age and more severe COPD .
A study investigated hoarseness/dysphonia in 313 patients with bronchial asthma using the fluticasone dry powder inhalers, showed that women complain of hoarseness and dysphonia more frequently than men. The authors highlighted the importance of selecting the most suitable device in this group in order to enhance the adherence . In a Chinese national pharmacy database (2191 men, 3313 women), men showed higher adherence to fluticasone treatment (23% in men vs. 21% in women) .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
In a study on inhalation technique using metered dose inhalers (33 men, 26 women), 75% of the participants had an incorrect inhalation technique, especially women, regardless of age. Only 4% of women and 43% of men had an acceptable inhalation technique. The authors speculate that this may add to the worse asthma prognosis in women, shown in a meta-analysis of six trials of randomly assigned asthma treatment .
Several studies have shown worse prognosis for women with asthma. In an observational registry study (416 men, 498 women), women were found to have more asthmatic symptoms, worse quality of life and require more health care due to their asthma . In a Danish prospective study on hospitalization due to asthma (6104 men of whom 2.5% had asthma, 7436 women of whom 2.2% had asthma), women had a 1.7 higher relative risk to be hospitalized . An observational study from Singapore found hospitalization due to asthma to be more common in boys than girls aged 0-4 years (boys/girls ratio 1.69). In adults aged 35-64 years, women were more hospitalized (men/women ratio 0.81) .
Date of litterature search: 2016-12-05
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson