Drug products: Assieme forte Turbuhaler, Assieme mite Turbuhaler, Assieme Turbuhaler, Bufomix Easyhaler, DuoResp Spiromax, Flutiform, Flutiform K-haler, Foradil HFA, Foradil®, Formatris Novolizer, Oxez Turbuhaler, Oxis Turbuhaler, Oxis® Turbuhaler®, Rilast forte Turbuhaler, Rilast Turbuhaler, Sinestic forte Turbuhaler, Sinestic Turbuhaler, Symbicort, Symbicort forte Turbuhaler, Symbicort mite Turbuhaler, Symbicort Turbuhaler, Symbicort® forte Turbuhaler®, Symbicort® mite Turbuhaler®, Symbicort® Turbuhaler®
ATC code: R03AC13, R03AK07, R03AK11
Substances: formoterol, formoterol fumarate dihydrate
One study in COPD patients treated with formoterol/budesonide showed that women had an increased risk of exacerbations. No sex differences in effect or pharmacokinetics have been observed.
One smaller study found women to have a poorer inhalation technique, thus risking lower effective dose.
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 [5, 6].
According to studies conducted by the manufacturer, no sex differences in pharmacokinetics have been identified for inhalation of either formoterol or budesonide [7, 8].
A randomized, open-label, crossover trial compared efficacy of formoterol and ipratropium/salbutamol in patients with chronic obstructive pulmonary disease (COPD) (49 men, 50 women). Post-hoc subgroup analyses showed that pre-dose FEV1 after two weeks was improved with formoterol when compared to ipratropium/salbutamol in men but not in women. Transition Dyspnea Index after two weeks was similar between treatments and in men and women .
A post hoc analysis of data from a randomized double-blind study in COPD patients (169 men, 86 women) showed that combination therapy of tiotropium and formoterol was more efficacious on FEV1 than tiotropium monotherapy in both men and women .
Except for events such as exacerbations in COPD no studies with a clinically relevant sex-analysis of adverse effects of formoterol have been found.
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) .Predictors for exacerbations in COPD patients was identified by analyzing data from clinical trials of formoterol/budesonide in patients with a history of exacerbations (2017 men, 1124 women). Multivariate analyses showed that female sex was one of the predictors of increased risk of exacerbations (HR 1.32). When data was analyzed separately for men and women, identified predictors in men were the same as for to the whole study population. In women, the same predictors were identified with the exceptions; ‘number of COPD exacerbations during the previous year’ was not one of the predictors while total score on the St George’s Respiratory Questionnaire was one .
Date of litterature search: 2017-05-27
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson