Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Ipratropium

Classification: A

Drug products: Atrovent, Atrovent Nasal, Atrovent®, Atrovent® Nasal, Combivent, Combivent®, Ipramol, Ipratropium/Salbutamol Orion, Ipratropium/Salbutamol Sandoz, Ipratropiumbromid Arrow, Ipratropiumbromid Ebb, Ipraxa, Itrop, Salipra, Sapimol

ATC code: R01AX03, R03AL02, R03BB01

Substances: ipratropium, ipratropium bromide, ipratropium bromide monohydrate

Summary

Larger studies with a clinically relevant analysis of sex differences are lacking. Two smaller studies have shown inconsistent results on sex differences.

One study has shown the risk of acute urinary retention to be higher in men compared to women treated with inhaled anticholinergic drugs, the risk was more pronounced in men with benign prostate hyperplasia.

One smaller study found women to have a poorer inhalation technique, thus risking lower effective dose.
 
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.

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

No studies with a clinically relevant sex analysis regarding the pharmacokinetics and dosing of ipratropium have been found.

Effects

Several studies have shown positive effects of ipratropium in addition to selective β2 agonists in the treatment of acute asthma [7, 8] compared to selective β2 agonists alone, while others have failed to show such an additive effect [9, 10]. No major studies with clinically relevant sex analysis regarding the effects of ipratropium have been found. A double-blind, randomized cross over, placebo-controlled study from 2002 (27 men, 17 women) with bronchial asthma, found however that men had a greater response (increase in FEV1) to ipratropium as compared to women [11]. An earlier study (11 men, 10 women) did not find such a difference [12].

Adverse effects

A nested case control study within a cohort of patients with chronic obstructive pulmonary disease (COPD) (cases: 178 men, 31 women; mean age 77 years) concluded that use of inhaled anticholinergic drugs, including ipratropium, increased the risk of acute urinary retention (AUR). The association was much stronger in men than in women. The risk of AUR was highest in men with benign prostatic hyperplasia. However, there were very few women cases [13]. 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) [14].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (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 868 men and 854 women on ipratropium) 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 [15]. 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: 2019-02-26

Date of litterature search: 2017-01-04

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. Garrett JE, Town GI, Rodwell P, Kelly AM. Nebulized salbutamol with and without ipratropium bromide in the treatment of acute asthma. J Allergy Clin Immunol. 1997;100:165-70. PubMed
  8. Lin RY, Pesola GR, Bakalchuk L, Morgan JP, Heyl GT, Freyberg CW et al. Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: a randomized clinical trial. Ann Emerg Med. 1998;31:208-13. PubMed
  9. FitzGerald JM, Grunfeld A, Pare PD, Levy RD, Newhouse MT, Hodder R et al. The clinical efficacy of combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma Canadian Combivent Study Group. Chest. 1997;111:311-5. PubMed
  10. Karpel JP, Schacter EN, Fanta C, Levey D, Spiro P, Aldrich T et al. A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma. Chest. 1996;110:611-6. PubMed
  11. Chhabra SK, Pandey KK. Comparison of acute bronchodilator effects of inhaled ipratropium bromide and salbutamol in bronchial asthma. J Asthma. 2002;39:375-81. PubMed
  12. Partridge MR, Saunders KB. Site of action of ipratropium bromide and clinical and physiological determinants of response in patients with asthma. Thorax. 1981;36:530-3. PubMed
  13. 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
  14. Cole JM, Sheehan AH, Jordan JK. Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease. Ann Pharmacother. 2012;46:1717-21. PubMed
  15. 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
  16. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2017-01-26.] länk

Authors: Helena Sundvall, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson