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Tiotropium Respimat® Soft Mist™ Inhaler: A Review of Its Use in Chronic Obstructive Pulmonary Disease

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Abstract

The long-acting anticholinergic agent tiotropium bromide (Spiriva®) is available as a solution for inhalation via Respimat® Soft Mist™ Inhaler in the EU and various other countries for the treatment of chronic obstructive pulmonary disease (COPD). With the Respimat® Soft Mist™ Inhaler there is improved lung deposition of drug (allowing a reduced dosage compared with tiotropium HandiHaler®), the delivered drug dose is independent of inspiratory effort and the prolonged duration of the aerosol cloud should make the co-ordination of actuation and inhalation easier. In patients with COPD, tiotropium Respimat® improved lung function, COPD exacerbations, health-related quality of life and dyspnoea and was at least as effective as tiotropium HandiHaler®. Tiotropium Respimat® was generally well tolerated in patients with COPD, with anticholinergic adverse events among the most commonly reported adverse events. In the TIOSPIR trial, tiotropium Respimat® was noninferior to tiotropium HandiHaler® in terms of all-cause mortality, and the risk of cardiovascular mortality or major adverse cardiovascular events did not significantly differ between the two treatment groups. In conclusion, tiotropium Respimat® Soft Mist™ Inhaler is a useful option for the treatment of patients with COPD.

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References

  1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: updated 2014. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html (2014). Accessed 22 Sep 2014.

  2. Barnes PJ. The pharmacological properties of tiotropium. Chest. 2000;117(2 Suppl):63S–6S.

    Article  PubMed  CAS  Google Scholar 

  3. Boehringer Ingelheim Limited. Spiriva (tiotropium) Respimat 2.5 micrograms, solution for inhalation: UK summary of product characteristics. 2014. http://www.medicines.org.uk/emc/medicine/20134/SPC/Spiriva+Respimat+2.5+micrograms+solution+for+inhalation/. Accessed 22 Sep 2014.

  4. Boehringer Ingelheim Limited. Spiriva (tiotropium) 18 microgram inhalation powder, hard capsule: UK summary of product characteristics. 2013. http://www.medicines.org.uk/emc/medicine/10039. Accessed 22 Sep 2014.

  5. Keating GM. Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs. 2012;72(2):273–300.

    Article  PubMed  Google Scholar 

  6. Dalby R, Spallek M, Voshaar T. A review of the development of Respimat® Soft Mist™ Inhaler. Int J Pharm. 2004;283(1–2):1–9.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  8. Hochrainer D, Hölz H, Kreher C, et al. Comparison of the aerosol velocity and spray duration of Respimat® Soft Mist™ inhaler and pressurized metered dose inhalers. J Aerosol Med. 2005;18(3):273–82.

    Article  PubMed  CAS  Google Scholar 

  9. Pitcairn G, Reader S, Pavia D, et al. Deposition of corticosteroid aerosol in the human lung by Respimat® Soft Mist™ inhaler compared to deposition by metered dose inhaler or by Turbuhaler® dry powder inhaler. J Aerosol Med. 2005;18(3):264–72.

    Article  PubMed  CAS  Google Scholar 

  10. Newman SP, Steed KP, Reader SJ, et al. Efficient delivery to the lungs of flunisolide aerosol from a new portable hand-held multidose nebulizer. J Pharm Sci. 1996;85(9):960–4.

    Article  PubMed  CAS  Google Scholar 

  11. Newman SP, Steed KP, Reader SJ, et al. An in vitro study to assess facial and ocular deposition from Respimat® Soft Mist™ inhaler. J Aerosol Med. 2007;20(1):7–12.

    Article  PubMed  CAS  Google Scholar 

  12. Medicines Evaluation Board. Public assessment report of the Medicines Evaluation Board in the Netherlands: Spiriva (tiotropium) Respimat 2.5 microgram, solution for inhalation. 2011. http://www.cbg-meb.nl/CBG/en/human-medicines/geneesmiddeleninformatiebank/default.htm. Accessed 22 Sep 2014.

  13. Disse B, Speck GA, Rominger KL, et al. Tiotropium (Spiriva™): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci. 1999;64(6–7):457–64.

    Article  PubMed  CAS  Google Scholar 

  14. Haddad E-B, Mak JCW, Barnes PJ. Characterization of [3H]Ba 679 BR, a slowly dissociating muscarinic antagonist, in human lung: radioligand binding and autoradiographic mapping. Mol Pharmacol. 1994;45(5):899–907.

    PubMed  CAS  Google Scholar 

  15. Disse B, Reichl R, Speck G, et al. BA 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci. 1993;52(5–6):537–44.

    Article  PubMed  CAS  Google Scholar 

  16. Tautermann CS, Kiechle T, Seeliger D, et al. Molecular basis for the long duration of action and kinetic selectivity of tiotropium for the muscarinic M3 receptor. J Med Chem. 2013;56(21):8746–56.

    Article  PubMed  CAS  Google Scholar 

  17. Takahashi T, Belvisi MG, Patel H, et al. Effect of BA 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. Am J Respir Crit Care Med. 1994;150(6 Pt 1):1640–5.

    Article  PubMed  CAS  Google Scholar 

  18. Sykes DA, Dowling MR, Leighton-Davies J, et al. The influence of receptor kinetics on the onset and duration of action and the therapeutic index of NVA237 and tiotropium. J Pharmacol Exp Ther. 2012;343(2):520–8.

    Article  PubMed  CAS  Google Scholar 

  19. van Noord JA, Cornelissen PJG, Aumann J-L, et al. The efficacy of tiotropium administered via Respimat® Soft Mist Inhaler™ or HandiHaler® in COPD patients. Respir Med. 2009;103(1):22–9.

    Article  PubMed  Google Scholar 

  20. Voshaar T, Lapidus R, Maleki-Yazdi R, et al. A randomized study of tiotropium Respimat® Soft Mist™ Inhaler vs. ipratropium pMDI in COPD. Respir Med. 2008;102(1):32–41.

    Article  PubMed  CAS  Google Scholar 

  21. Ichinose M, Fujimoto T, Fukuchi Y. Tiotropium 5 μg via Respimat and 18 μg via HandiHaler; efficacy and safety in Japanese COPD patients. Respir Med. 2010;104(2):228–36.

    Article  PubMed  CAS  Google Scholar 

  22. Hohlfeld JM, Sharma A, van Noord JA, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–14.

    Article  PubMed  CAS  Google Scholar 

  23. Bateman E, Singh D, Smith D, et al. Efficacy and safety of tiotropium Respimat® SMI in COPD in two 1-year randomized studies. Int J Chron Obstruct Pulmon Dis. 2010;5:197–208.

    PubMed  CAS  PubMed Central  Google Scholar 

  24. Bateman ED, Tashkin D, Siafakas N, et al. A one-year trial of tiotropium Respimat® plus usual therapy in COPD patients. Respir Med. 2010;104(10):1460–72.

    Article  PubMed  CAS  Google Scholar 

  25. Feifel U, Wallenstein G, Rominger K-L, et al. Pharmacokinetics and tolerability (study 1) with particular reference to ocular safety (study 2) of tiotropium Respimat® Soft Mist Inhaler™: findings from two dose-ranging studies in healthy men. Int J Chron Obstruct Pulmon Dis. 2008;3(3):397–403.

    PubMed  CAS  PubMed Central  Google Scholar 

  26. Asano K, Shikama Y, Shibuya Y, et al. Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro. Int J Chron Obstruct Pulmon Dis. 2008;3(4):781–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  27. Asano K, Shikama Y, Shoji N, et al. Tiotropium bromide inhibits TGF-β-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro. Int J Chron Obstruct Pulmon Dis. 2010;5:277–86.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Powrie DJ, Wilkinson TMA, Donaldson GC, et al. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J. 2007;30(3):472–8.

    Article  PubMed  CAS  Google Scholar 

  29. Holownia A, Mroz RM, Skopinski T, et al. Tiotropium increases PPARγ and decreases CREB in cells isolated from induced sputum of COPD patients. Adv Exp Med Biol. 2013;756:9–14.

    Article  PubMed  CAS  Google Scholar 

  30. Caillaud D, Le Merre C, Martinat Y, et al. A dose-ranging study of tiotropium delivered via Respimat® Soft Mist Inhaler™ or HandiHaler® in COPD patients. Int J Chron Obstruct Pulmon Dis. 2007;2(4):559–65.

    PubMed  CAS  PubMed Central  Google Scholar 

  31. Nakanishi T, Haruta T, Shirasaka Y, et al. Organic cation transporter-mediated renal secretion of ipratropium and tiotropium in rats and humans. Drug Metab Dispos. 2011;39(1):117–22.

    Article  PubMed  CAS  Google Scholar 

  32. Sharma A, Hohlfeld J, Cornelissen PJG, et al. Comparison of the pharmacokinetics and pharmacodynamics of once daily tiotropium Respimat® and tiotropium HandiHaler® in COPD patients [slide presentation]. In: European Respiratory Society Annual Congress 2013; 7–11 Sep 2013; Barcelona.

  33. Calverley P, Könen-Bergmann M, Metzdorf N, et al. Tiotropium Respimat®: comparison of bronchodilator efficacy of 5- and 2.5-μg doses [abstract no. P924 plus poster]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  34. Tang Y, Massey D, Zhong N-S. Evaluation of the efficacy and safety of tiotropium bromide (5 μg) inhaled via Respimat in Chinese patients with chronic obstructive pulmonary disease. Chin Med J. 2013;126(19):3603–7.

    PubMed  CAS  Google Scholar 

  35. Wise RA, Anzueto A, Cotton D, et al. Tiotropium respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369(16):1491–501.

    Article  PubMed  CAS  Google Scholar 

  36. Rau-Berger H, Mitfessel H, Glaab T. Tiotropium Respimat® improves physical functioning in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:367–73.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Hodder R, Pavia D, Lee A, et al. Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD. Int J Chron Obstruct Pulmon Dis. 2011;6:245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Tashkin D, Metzdorf N, Hallmann C, et al. Safety of tiotropium in renally impaired patients [abstract no. P923 plus poster]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  39. Hohlfeld JM, Furtwaengler A, Könen-Bergmann M, et al. Cardiac safety of tiotropium in patients with COPD: combined analysis of Holter-ECG data from four randomized clinical trials [abstract no. P284 plus poster]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  40. Boehringer Ingelheim. Boehringer Ingelheim announces FDA approval of Spiriva® Respimat® (tiotropium bromide) inhalation spray for the maintenance treatment of COPD [media release]. 25 Sep 2014. http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/09-25-14-boehringer-ingelheim-announces-fda-approval-spiriva-respimat-tiotropium-bromide-inhalation-spray-maintenance-treatment-copd.html.

  41. Data on file, Boehringer Ingelheim: 2014.

  42. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Evangelopoulou E, et al. Comparative mortality risk of tiotropium administered via handihaler or respimat in COPD patients: are they equivalent? Pulm Pharmacol Ther. 2014;28(2):91–7.

    Article  PubMed  CAS  Google Scholar 

  43. US Food and Drug Administration. Early communication about an ongoing safety review of tiotropium (marketed as Spiriva HandiHaler). 2008. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070651.htm. Accessed 22 Sep 2014.

  44. Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2008;300(12):1439–50.

    Article  PubMed  CAS  Google Scholar 

  45. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54.

    Article  PubMed  CAS  Google Scholar 

  46. US Food and Drug Administration. Follow-up to the October 2008 updated early communication about an ongoing safety review of tiotropium (marketed as Spiriva HandiHaler). 2010. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm197429.htm. Accessed 22 Sep 2014.

  47. Rodrigo GJ, Castro-Rodriguez JA, Nannini LJ, et al. Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis. Respir Med. 2009;103(10):1421–9.

    Article  PubMed  Google Scholar 

  48. Celli B, Decramer M, Leimer I, et al. Cardiovascular safety of tiotropium in patients with COPD. Chest. 2010;137(1):20–30.

    Article  PubMed  CAS  Google Scholar 

  49. Kesten S, Celli B, Decramer M, et al. Tiotropium HandiHaler® in the treatment of COPD: a safety review. Int J Chron Obstruct Pulmon Dis. 2009;4:397–409.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Bateman ED. Tiotropium Respimat increases the risk of mortality: con. Eur Respir J. 2013;42(3):590–3.

    Article  PubMed  CAS  Google Scholar 

  51. Singh S, Loke YK, Enright PL, et al. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2011;342:d3215.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Dong Y-H, Lin H-H, Shau W-Y, et al. Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax. 2013;68(1):48–56.

    Article  PubMed  Google Scholar 

  53. Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7: CD009285.

  54. Verhamme KMC, Afonso A, Romio S, et al. Use of tiotropium Respimat Soft Mist Inhaler versus HandiHaler and mortality in patients with COPD. Eur Respir J. 2013;42(3):606–15.

    Article  PubMed  CAS  Google Scholar 

  55. Disse B, Metzdorf N, Martin A, et al. Mortality associated with tiotropium mist inhaler? A critical appraisal of the authors’ selection and use of previously communicated tiotropium Respimat data [letter]. 2011. http://www.bmj.com/content/342/bmj.d3215?tab=responses. Accessed 22 Sep 2014.

  56. Metzdorf N, Hallmann C, Disse B. Thorax editorial by Jenkins and Beasley related to tiotropium respimat [letter]. Thorax. 2013;68(8):782.

    Article  PubMed  Google Scholar 

  57. Barnes NC, Jones PW, Davis KJ. Safety of tiotropium through the Handihaler: why did meta-analyses and database studies appear to give a false alarm? Thorax. 2014;69(6):598–9.

    Article  PubMed  Google Scholar 

  58. European Medicines Agency. Pharmacovigilance Risk Assessment Committee (PRAC): PRAC minutes of the meeting on 2-5 December 2013. 2013. www.ema.europa.eu/docs/en_GB/document_library/Minutes/2014/01/WC500159614.pdf. Accessed 22 Sep 2014.

  59. European Medicines Agency. Pharmacovigilance Risk Assessment Committee (PRAC): minutes of the meeting on 5-8 May 2014. 2014. www.ema.europa.eu/docs/en_GB/document_library/Minutes/2014/06/WC500169468.pdf. Accessed 22 Sep 2014.

  60. Verhamme KMC, Van Blijderveen N, Sturkenboom MCJM. Tiotropium and the risk of death in COPD [letter]. N Engl J Med. 2014;370(5):481–2.

    PubMed  Google Scholar 

  61. Halpin D, Dahl R, Hallmann C, et al. Tiotropium Handihaler® and Respimat® in COPD: a safety analysis on pooled data [abstract]. In: American Thoracic Society 2014 International Conference; 16–21 May 2014; San Diego (CA).

  62. Dahl R, Schmidt H, Könen-Bergmann M, et al. Mixed treatment analysis comparing tiotropium HandiHaler® and Respimat® [abstract no. P925 plus poster]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  63. Bateman ED. Improving inhaler use in COPD and the role of patient preference. Eur Respir Rev. 2005;14(96):85–8.

    Article  Google Scholar 

  64. Anderson P. Use of Respimat® Soft Mist™ Inhaler in COPD patients. Int J Chron Obstruct Pulmon Dis. 2006;1(3):251–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  65. Fink JB, Colice GL, Hodder R. Inhaler devices for patients with COPD. COPD. 2013;10(4):523–35.

    Article  PubMed  Google Scholar 

  66. Beasley R. Tiotropium Respimat increases the risk of mortality: pro. Eur Respir J. 2013;42(3):584–9.

    Article  PubMed  CAS  Google Scholar 

  67. Asakura Y, Nishimura N, Maezawa K, et al. Effect of switching tiotropium HandiHaler® to Respimat® Soft Mist™ Inhaler in patients with COPD: the difference of adverse events and usability between inhaler devices. J Aerosol Med Pulm Drug Deliv. 2013;26(1):41–5.

    Article  PubMed  CAS  Google Scholar 

  68. Shah P, Dhurjon L, Metcalfe T, et al. Acute angle closure glaucoma associated with nebulised ipratropium bromide and salbutamol. BMJ. 1992;304(6818):40–1.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  69. Oksuz H, Tamer C, Akoglu S, et al. Acute angle-closure glaucoma precipitated by local tiotropium absorption. Pulm Pharmacol Ther. 2007;20(6):627–8.

    Article  PubMed  CAS  Google Scholar 

  70. Hall SK. Acute angle-closure glaucoma as a complication of combined beta-agonist and ipratropium bromide therapy in the emergency department. Ann Emerg Med. 1994;23(4):884–7.

    Article  PubMed  CAS  Google Scholar 

  71. Boehringer Ingelheim. Tiotropium + olodaterol fixed dose combination (FDC) in chronic obstructive pulmonary disease (OTEMTO 2) [ClinicalTrials.gov identifier NCT02006732] US National Institutes of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT02006732. Accessed 22 Sep 2014.

  72. Boehringer Ingelheim. Tiotropium + olodaterol fixed dose combination (FDC) in chronic obstructive pulmonary disease (OTEMTO 1) [ClinicalTrials.gov identifier NCT01964352] US National Institutes of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT01964352. Accessed 22 Sep 2014.

  73. Derom E, Westerman J, Grönke L, et al. The 24-hour lung function profile of once-daily tiotropium and olodaterol fixed-dose combination compared with placebo and monotherapies in chronic obstructive pulmonary disease (VIVACITO) [poster]. In: American Thoracic Society International Conference; 16–21 May 2014; San Diego (CA).

  74. Buhl R, Derom E, Ferguson G, et al. Once-daily tiotropium and olodaterol fixed-dose combination via the Respimat improves ouctomes vs monocomponents in COPD in two 1-year studies [abstract no. 1895]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  75. Buhl R, Abrahams R, Bjermer L, et al. Safety of once-daily tiotropium and olodaterol fixed-dose combination via the Respimat® in chronic obstructive pulmonary disease in two 1-year studies [poster]. In: European Respiratory Society International Congress 2014; 6–10 Sep 2014; Munich.

  76. Yohannes AM, Connolly MJ, Hanania NA. Ten years of tiotropium: clinical impact and patient perspectives. Int J Chron Obstruct Pulmon Dis. 2013;8:117–25.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Disclosure

The preparation of this review was not supported by any external funding. Gillian Keating is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Gillian M. Keating

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The manuscript was reviewed by: S.A. Antoniu, University of Medicine and Pharmacy Grigore T Popa Iasi, Department of Interdisciplinarity-Palliative Care Nursing, Iasi, Romania; M. Confalonieri, Department of Pneumology & Respiratory Intensive Care Unit, University Hospital of Cattinara, Trieste, Italy; F. García-Río, Servicio de Neumología, Hospital Universitario La Paz, Facultad de Medicina, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain; C. Incorvaia, Pulmonary Rehabilitation Unit, Istituti Clinici di Perfezionamento, Presidio Ospedaliero CTO, Milan, Italy.

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Keating, G.M. Tiotropium Respimat® Soft Mist™ Inhaler: A Review of Its Use in Chronic Obstructive Pulmonary Disease. Drugs 74, 1801–1816 (2014). https://doi.org/10.1007/s40265-014-0307-4

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