Drug products: Aerivio Spiromax, Airflusal Forspiro, Brisomax Diskus, Brisomax Diskus forte, Novucaeli, Relanio, Salflumix Easyhaler, Salmeterol/Fluticasone Abacus Medicine, Salmeterol/Fluticasone Cipla, Salmeterol/Fluticasone Neutec, 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, Serevent Diskus, Serevent Evohaler, Serevent® Diskus®, Serevent® Evohaler®, Veraspir Diskus
ATC code: R03AC12, R03AK06
Substances: salmeterol, salmeterol xinafoate
Salmeterol in combination with fluticasone have similar effect and in men and women with chronic obstructive pulmonary disease. No sex differences in adverse event frequency have been reported.
A smaller study found generally poorer inhalation technique in women leading to lower effective dose.
Pharmacokinetics and dosing
In a population pharmacokinetic analysis in healthy individuals (n=57) were given single dose of fluticasone/salmeterol 500/50 µg. Men had higher clearance than women . The clinical relevance of this difference is unclear.
Difference between men and women in effects in the efficacy of salmeterol 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.
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 frequency of adverse events from salmeterol/fluticasone combination treatment for COPD was similar in men and women .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (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: 2018-11-19
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- Osborne ML, Vollmer WM, Linton KL, Buist AS. Characteristics of patients with asthma within a large HMO: a comparison by age and gender. Am J Respir Crit Care Med. 1998;157:123-8. PubMed
- Prescott E, Lange P, Vestbo J. Effect of gender on hospital admissions for asthma and prevalence of self-reported asthma: a prospective study based on a sample of the general population Copenhagen City Heart Study Group. Thorax. 1997;52:287-9. PubMed
- Ng TP, Niti M, Tan WC. Trends and ethnic differences in asthma hospitalization rates in Singapore, 1991 to 1998. Ann Allergy Asthma Immunol. 2003;90:51-5. PubMed
- Soulele K, Macheras P, Silvestro L, Rizea Savu S, Karalis V. Population pharmacokinetics of fluticasone propionate/salmeterol using two different dry powder inhalers. Eur J Pharm Sci. 2015;80(1):33-42. PubMed
- Vestbo J, Soriano JB, Anderson JA, Calverley P, Pauwels R, Jones P et al. Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD. Respir Med. 2004;98:1045-50. PubMed
- Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361:449-56. PubMed
- Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775-89. PubMed
- Celli B, Vestbo J, Jenkins CR, Jones PW, Ferguson GT, Calverley PM et al. Sex differences in mortality and clinical expressions of patients with chronic obstructive pulmonary disease The TORCH experience. Am J Respir Crit Care Med. 2011;183:317-22. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-12-17.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson