Drug products: Assieme forte Turbuhaler, Assieme mite Turbuhaler, Assieme Turbuhaler, Bevespi Aerosphere, Bufomix Easyhaler, Duaklir Genuair, Dulera, DuoResp Spiromax, Flutiform, Flutiform K-haler, Foradil HFA, Foradil®, Formatris Novolizer, Innovair, Innovair nexthaler, Oxez Turbuhaler, Oxis Turbuhaler, Oxis® Turbuhaler®, Rilast forte Turbuhaler, Rilast Turbuhaler, Sinestic forte Turbuhaler, Sinestic Turbuhaler, Symbicort, Symbicort Turbuhaler, Symbicort forte Turbuhaler, Symbicort mite Turbuhaler, Symbicort Turbuhaler, Symbicort® forte Turbuhaler®, Symbicort® mite Turbuhaler®, Symbicort® Turbuhaler®, Trimbow, Trixeo Aerosphere
ATC code: R03AC13, R03AK07, R03AK08, R03AK09, R03AK11, R03AL05, R03AL07, R03AL09, R03AL11
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].
Pharmacokinetics and dosing
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.
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) .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
- Goodman DE, Israel E, Rosenberg M, Johnston R, Weiss ST, Drazen JM. The influence of age, diagnosis, and gender on proper use of metered-dose inhalers. Am J Respir Crit Care Med. 1994;150:1256-61. PubMed
- 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
- Dales RE, Mehdizadeh A, Aaron SD, Vandemheen KL, Clinch J. Sex differences in the clinical presentation and management of airflow obstruction. Eur Respir J. 2006;28:319-22. PubMed
- Tantisira KG, Colvin R, Tonascia J, Strunk RC, Weiss ST, Fuhlbrigge AL et al. Airway responsiveness in mild to moderate childhood asthma: sex influences on the natural history. Am J Respir Crit Care Med. 2008;178:325-31. PubMed
- Symbicort (budesonide/formoterol). DailyMed [www]. [updated 2017-01-27, cited 2017-05-27]. länk
- Food and Drug Aministration (FDA) . Clinical Pharmacology and Biopharmaceutics Review - SYMBICORT (budesonide/formoterol). Food and Drug Aministration [www]. [updated 2006-07-21, cited 2017-05-27]. länk
- Sutherland ER, Brazinsky S, Feldman G, McGinty J, Tomlinson L, Denis-Mize K. Nebulized formoterol effect on bronchodilation and satisfaction in COPD patients compared to QID ipratropium/albuterol MDI. Curr Med Res Opin. 2009;25:653-61. PubMed
- Tashkin DP, Varghese ST. Combined treatment with formoterol and tiotropium is more efficacious than treatment with tiotropium alone in patients with chronic obstructive pulmonary disease, regardless of smoking status, inhaled corticosteroid use, baseline severity, or gender. Pulm Pharmacol Ther. 2011;24:147-52. PubMed
- Make BJ, Eriksson G, Calverley PM, Jenkins CR, Postma DS, Peterson S et al. A score to predict short-term risk of COPD exacerbations (SCOPEX). Int J Chron Obstruct Pulmon Dis. 2015;10:201-9. PubMed
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson