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Tiotropium

Classification: A

Drug products: Braltus, Spiolto Respimat, Spiriva, Spiriva Respimat, Spiriva®, Tiogiva

ATC code: R03AL06, R03BB04

Substances: tiotropium, tiotropium bromide, tiotropium bromide monohydrate

Summary

The effect of tiotropium has shown to be similar in men and women. Acute urinary retention has been reported more in men.

One smaller study found women to have a poorer inhalation technique, thus risking lower effective dose.

Additional information

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 the manufacturer’s documentation to the FDA, no relevant sex differences in drug plasma concentrations or urinary excretion of tiotropium were seen [7]. AUC and Cmax were 17% and 34% higher in women, but was considered comparable between the sexes in the range of variability [8].

Effects

Randomized double-blind placebo-controlled trials conducted by the manufacturer (in total 3476 asthma patients), adult men and women receiving tiotropium in different doses had similar FEV1 response [9].

Subgroup analysis of data from the UPLIFT trial, a randomized, double-blind, placebo-controlled trial of tiotropium in COPD patients (4473 men, 1519 women), showed that tiotropium had similar benefits in men and women. There were no sex differences in reduced risk of an exacerbation, improvement in health-related quality of life (HRQL) or mortality during treatment [10].

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 [11].

Adverse effects

A case-control study of the association between inhaled anticholinergic drugs and acute urinary retention in COPD patients (cases 178 men, 31 women; mean age 77 years) found a stronger association in men than in women (1.73 vs 073). However, there were very few women cases [12]. Similarly, a review of concomitant use of ipratropium and tiotropium showed a higher risk of acute urinary retention in men than women (9432 men, 1806 women) [13].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

A Dutch registry study including new users of tiotropium, ipratropium, long-acting beta-agonists, or fixed combination of LABA and inhaled corticosteroids (in total 2737 men and 2583 women, of which 599 men and 429 women on tiotropium) showed that men with COPD persisted with inhalation treatment more than women. These drugs included ipratropium, tiotropium, long-acting beta agonists and short-acting beta agonists [14]. 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 [1].

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 [2]. 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 [3]. 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) [4].

Updated: 2020-08-28

Date of litterature search: 2017-05-24

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. Food and Drug Aministration (FDA). Clinical Pharmacology and Biopharmaceutics Review - SPIRIVA (tiotropium bromide inhalation powder). Food and Drug Aministration [www]. [updated 2004-01-30, cited 2017-05-24]. länk
  8. Food and Drug Aministration (FDA). Clinical Pharmacology and Biopharmaceutics Review - SPIRIVA RESPIMAT (tiotropium bromide inhalation spray). Food and Drug Aministration [www]. [updated 2014-09-24, cited 2017-05-24]. länk
  9. SPIRIVA RESPIMAT (tiotropium bromide) inhalation spray. DailyMed [www]. US National Library of Medicine. [updated 2017-02-27, cited 2014-05-26]. länk
  10. Tashkin D, Celli B, Kesten S, Lystig T, Decramer M. Effect of tiotropium in men and women with COPD: results of the 4-year UPLIFT trial. Respir Med. 2010;104:1495-504. PubMed
  11. 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
  12. Afonso AS, Verhamme KM, Stricker BH, Sturkenboom MC, Brusselle GG. Inhaled anticholinergic drugs and risk of acute urinary retention. BJU Int. 2011;107:1265-72. PubMed
  13. Cole JM, Sheehan AH, Jordan JK. Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease. Ann Pharmacother. 2012;46:1717-21. PubMed
  14. Breekveldt-Postma NS, Koerselman J, Erkens JA, Lammers JW, Herings RM. Enhanced persistence with tiotropium compared with other respiratory drugs in COPD. Respir Med. 2007;101:1398-405. PubMed
  15. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2016 [cited 2017-05-20.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson