Skip to main content
SpringerLink
Log in

A Review of Ipratropium Bromide/Fenoterol Hydrobromide (Berodual®) Delivered Via Respimat® Soft Mist™ Inhaler in Patients with Asthma and Chronic Obstructive Pulmonary Disease

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual® is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the β2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years.

The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluoro-carbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat® Soft Mist™ Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist™) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI.

A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat® SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5μg to 320/800μg via Respimat® SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat® SMI. In the phase III studies, each dose from Respimat® SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device.

The results of the trials demonstrated that IB/FEN via Respimat® SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat® SMI obviates the need for a spacer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Fig. 3
Table II
Table III
Fig. 4
Table IV
Table V

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Nicklas RA. National and international guidelines for the diagnosis and treatment of asthma. Curr Opin Pulm Med 1997; 3: 51–5

    Article  PubMed  CAS  Google Scholar 

  2. British Thoracic Society, National Asthma Campaign, Royal College of Physicians of London. The British guidelines on asthma management. Thorax 1997; 52: S1–21

    Article  Google Scholar 

  3. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152: S77–121

    Google Scholar 

  4. National Institutes of Health; National Heart, Lung and Blood Institute. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Report of NHLBI/WHO Workshop, April1998. Updated 2003 [online]. Available from URL: http://www.goldcopd.com [Accessed 2004 Mar 1]

  5. National Institutes of Health. Global Initiative for Asthma. Global strategy for asthma management and prevention: NHLBI/WHO Workshop Report. Bethesda (MD): National Institutes of Health, National Heart Lung and Blood Institute; 2002 Apr. Publication no.: 02-3659

  6. Pavia D. Efficacy and safety of inhalation therapy in chronic obstructive pulmonary disease and asthma. Respirology 1997; 2 Suppl. 1: S5–10

    PubMed  Google Scholar 

  7. Newman SP, Brown J, Steed KP, et al. Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines. Chest 1998; 113: 957–63

    Article  PubMed  CAS  Google Scholar 

  8. Kunkel G, Magnussen H, Bergmann KC, et al. Respimat® (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients. Respiration 2000; 67: 306–14

    Article  PubMed  CAS  Google Scholar 

  9. Ganderton D. Targeted delivery of inhaled drugs: current challenges and future goals. J Aerosol Med 1999; 12 Suppl. 1: S3–8

    PubMed  Google Scholar 

  10. Lötvall J, O’Byrne P. Targeting drugs to the airways by different inhalation devices. Biodrugs 1999; 12: 279–89

    Article  PubMed  Google Scholar 

  11. Goldberg J, Freund E, Beckers B, et al. Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler. Eur Respir J 2001; 17: 225–32

    Article  PubMed  CAS  Google Scholar 

  12. Vincken W, Bantje T, Middle MV, et al. Long-term efficacy and safety of ipratropium bromide plus fenoterol via Respimat® Soft Mist® Inhaler (SMI) versus a pressurised metered dose inhaler in asthma. Clin Drug Invest 2004; 24(1): 17–28

    Article  CAS  Google Scholar 

  13. von Berg A, Jeena PM, Soemantri PA, et al. Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat® Soft Mist™ Inhaler vs a conventional metered dose inhaler plus spacer in children with asthma. Pediatr Pulmonol 2004; 37: 264–72

    Article  Google Scholar 

  14. Kilfeather SA, Ponitz HH, Beck E, et al. Improved delivery of ipratropium bromide/fenoterol from Respimat® Soft Mist™ Inhaler in patients with COPD. Respir Med 2004; 98: 387–97

    Article  PubMed  CAS  Google Scholar 

  15. Hodder R, Pavia DD, Dewberry HM, et al. Comparison of the safety relating to paradoxical bronchoconstriction of ipratropium bromide (IB) alone or combined with fenoterol hydrobromide (FEN) inhaled from a new soft mist inhaler (SMI) and from a conventional metered dose inhaler (CFC-MDI) in asthma and COPD patients [abstract]. Eur Respir J 2002; 20 Suppl. 38: 246s

  16. Traunecker W, Muacevic G. Pharmacological effects of a combination of fenoterol hydrobromide and ipratropium bromide. Respiration 1986; 50(4): 244–51

    Article  PubMed  CAS  Google Scholar 

  17. Molkenboer JFWM, Cornelissen PJG. A double-blind randomised cross-over study assessing the efficacy of Berodual in comparison to its components ipratropium bromide and fenoterol in chronic bronchitis. Postgrad J Med 1987; 64: 19a-20a

    Google Scholar 

  18. O’Donnell DE, Aaron S, Bourbeau J, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease. Can Respir J 2003; 10: Suppl. A: 11A–65A

    PubMed  Google Scholar 

  19. Frolund L, Madsen F, Svendsen UG, et al. Comparison of two aerosols containing both fenoterol and ipratropium in a high (Duovent®) and low (Berodual®) concentration, respectively. Respiration 1986; 50 Suppl. 2: 270–3

    Google Scholar 

  20. Philip-Joet F, Reynaud-Gaubert M, Jirou-Najou JL, et al. Comparison of Berodual® and salbutamol in asthma: a multicenter evaluation. Respiration 1990; 57: 379–83

    Article  PubMed  CAS  Google Scholar 

  21. Jedrys U, Kurzawa R, Haluszka J, et al. Evaluation of the bronchodilatory activity of Berodual® and its components: fenoterol and ipratropium bromide in children with bronchial asthma [in Polish]. Pneumonol Alergol Pol 1994; 62: 615–22

    PubMed  CAS  Google Scholar 

  22. Baculard A. Role of Bronchodual in the long-term treatment of asthma in children [in French]. Arch Pediatr 1995; 2 Suppl. 2: S149–53

    Article  Google Scholar 

  23. Ciappi G, Magnini P, Valente S, et al. Dose-response relationship: fenoterol, ipratropium bromide and their combination. Respiration 1986; 50 Suppl. 2: 140–3

    Article  Google Scholar 

  24. Serra C, Giacopelli A, Luciani G. Acute controlled study of the dose-response relationship of fenoterol, ipratropium bromide and their combination. Respiration 1986; 50 Suppl. 2: 144–7

    Article  Google Scholar 

  25. Duerden M, Price D. Training issues in the use of inhalers. Dis Manag Health Outcomes 2001; 9: 75–87

    Article  Google Scholar 

  26. Erickson SR, Horton A, Kirking DM. Assessing metered-dose inhaler technique: comparison of observation vs patient self-report. J Asthma 1998; 35: 575–83

    Article  PubMed  CAS  Google Scholar 

  27. Larsen JS, Hahn M, Kockevar JW, et al. Administration errors with a conventional metered dose inhaler versus a novel breath actuated device. Ann Allergy 1993; 71: 103–6

    PubMed  CAS  Google Scholar 

  28. Zierenberg B, Eicher J, Dunne S, Freund B. Boehringer Ingelheim nebulizer BINEB®: a new approach to inhalation therapy. In: Dalby RN, Byron PR, Farr SJ, editors. Respiratory Drug Delivery V. Buffalo Grove (IL): Interpharm Press, 1996: 187–93

    Google Scholar 

  29. Zierenberg B. Optimizing the in vitro performance of the Respimat®. J Aerosol Med 1999; 12 Suppl. 1: S19–24

    Article  PubMed  Google Scholar 

  30. Spallek M, Hochrainer D, Wachtel H. Optimizing nozzles for soft mist inhalers. Respiratory Drug Delivery VIII 2002; 2: 375–8

    Google Scholar 

  31. Newman SP, Steed KP, Reader SJ, et al. Efficient delivery to the lungs of flunisolide aerosol from a new portable hand-held multidose nebuliser. J Pharm Sci 1996; 85: 960–4

    Article  PubMed  CAS  Google Scholar 

  32. Steed KP, Towse LJ, Freund B, et al. Lung and oropharyngeal depositions of fenoterol hydrobromide delivered from the prototype III hand-held multidose Respimat® nebuliser. Eur J Pharm Sci 1997; 5: 55–61

    Article  CAS  Google Scholar 

  33. Littner M, Taylor JR, Ghafouri M, et al. A dose ranging study of ipratropium bromide solution delivered via a novel soft mist inhaler in patients with chronic obstructive pulmonary disease (COPD). Eur Respir J 2000; 16 Suppl. 31: 55S

  34. van Noord JA, Smeets JJ, Creemers JPHM, et al. Delivery of fenoterol via Respimat®, a novel ‘soft mist’ inhaler: a randomised, double-blind (within device), placebo-controlled, crossover, dose-ranging study in asthmatic patients. Respiration 2000; 67: 672–8

    Article  PubMed  Google Scholar 

  35. Maesen FPV, Greefhorst LPM, Smeets JJ, et al. Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual®) for the delivery of a fixed combination of fenoterol/ ipratropium bromide. Respiration 1997; 64: 273–80

    Article  PubMed  CAS  Google Scholar 

  36. Morrison JFJ, Jones PC, Muers MF. Assessing physiological benefit from domiciliary nebulized bronchodilators in severe airflow limitation. Eur Respir J 1992; 5: 424–9

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This review was sponsored by Boehringer Ingelheim.

Author information

Authors and Affiliations

  1. Pneumologisches Zentrum Cottbus, Groβ, Gaglow, Germany

    Frank Kässner

  2. Divisions of Pulmonary and Critical Care Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Rick Hodder

  3. UCT Lung Institute, University of Cape Town, Cape Town, South Africa

    Eric D. Bateman

Authors
  1. Frank Kässner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rick Hodder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric D. Bateman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kässner, F., Hodder, R. & Bateman, E.D. A Review of Ipratropium Bromide/Fenoterol Hydrobromide (Berodual®) Delivered Via Respimat® Soft Mist™ Inhaler in Patients with Asthma and Chronic Obstructive Pulmonary Disease . Drugs 64, 1671–1682 (2004). https://doi.org/10.2165/00003495-200464150-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200464150-00005

Keywords

Search

Navigation