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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2016

Open Access 01-12-2016 | Research article

A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?

Authors: Ronald Dahl, Alan Kaplan

Published in: BMC Pulmonary Medicine | Issue 1/2016

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Abstract

Background

In many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD). Tiotropium Respimat® is a propellant-free, multi-dose inhaler that delivers a metered dose of medication as a fine, slow-moving, long-lasting soft mist, independently of patient inspiratory effort. The high fine-particle fraction of droplets produced by the Respimat® inhaler optimizes the efficiency of drug delivery to the lungs.

Methods

To help inform the choice of tiotropium inhaler for prescribers and patients, this systematic review summarizes the available pharmacokinetic, efficacy and safety data from comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in COPD, focusing on the licensed once-daily doses of 5 and 18 μg, respectively. Data sources reviewed include publications and abstracts identified from database searches.

Results

Published evidence from comparative studies suggests that tiotropium Respimat® 5 μg and tiotropium HandiHaler® 18 μg provide similar clinical outcomes in patients with COPD.

Conclusions

The findings indicate that physicians can base their decision about an inhaler for tiotropium on factors other than efficacy or safety. These could be patient preference for a particular inhaler, ease of use and the efficiency of drug delivery, with the aim of optimizing adherence and clinical outcomes with long-term tiotropium maintenance therapy.
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Literature
1.
Makela MJ, Backer V, Hedegaard M, Larsson K. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD. Respir Med. 2013;107:1481–90.CrossRefPubMed
2.
SPIRIVA® HandiHaler® (tiotropium bromide inhalation powder) capsules for respiratory inhalation [prescribing information]. Ridgefield, CT, USA: Boehringer Ingelheim Pharmaceuticals Inc. 2014.
3.
4.
SPIRIVA® Respimat® (tiotropium bromide) inhalation spray: for oral inhalation [prescribing information]. Ridgefield, CT, USA: Boehringer Ingelheim Pharmaceuticals, Inc. 2015.
5.
6.
7.
Keating GM. Tiotropium Respimat(®) Soft Mist inhaler: a review of its use in chronic obstructive pulmonary disease. Drugs. 2014;74:1801–16.CrossRefPubMed
8.
Health Canada. PrSTRIVERDI RESPIMAT. 17-6-2014.
9.
Brand P, Meyer T, Weuthen T, Timmer W, Berkel E, Wallenstein G, et al. Lung deposition of radiolabeled tiotropium in healthy subjects and patients with chronic obstructive pulmonary disease. J Clin Pharmacol. 2007;47:1335–41.CrossRefPubMed
10.
Chodosh S, Flanders JS, Kesten S, Serby CW, Hochrainer D, Witek TJJ. Effective delivery of particles with the HandiHaler dry powder inhalation system over a range of chronic obstructive pulmonary disease severity. J Aerosol Med. 2001;14:309–15.CrossRefPubMed
11.
Dalby RN, Eicher J, Zierenberg B. Development of Respimat® Soft Mist Inhaler and its clinical utility in respiratory disorders. Med Devices (Auckl). 2011;4:145–55.
12.
13.
Hochrainer D, Holz H, Kreher C, Scaffidi L, Spallek M, Wachtel H. Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers. J Aerosol Med. 2005;18:273–82.CrossRefPubMed
14.
Pitcairn G, Reader S, Pavia D, Newman S. 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;18:264–72.CrossRefPubMed
15.
Zierenberg B. Optimizing the in vitro performance of Respimat. J Aerosol Med. 1999;12 Suppl 1:S19–24.PubMed
16.
Capstick TG, Clifton IJ. Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma. Expert Rev Respir Med. 2012;6:91–101.CrossRefPubMed
17.
Lippmann M, Yeates DB, Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med. 1980;37:337–62.PubMedPubMedCentral
18.
Dalby R, Spallek M, Voshaar T. A review of the development of Respimat Soft Mist Inhaler. Int J Pharm. 2004;283:1–9.CrossRefPubMed
19.
Newman SP, Steed KP, Reader SJ, Hooper G, Zierenberg B. Efficient delivery to the lungs of flunisolide aerosol from a new portable hand-held multidose nebulizer. J Pharm Sci. 1996;85:960–4.CrossRefPubMed
20.
Ninane V, Vandevoorde J, Cataldo D, Derom E, Liistro G, Munghen E, et al. New developments in inhaler devices within pharmaceutical companies: A systematic review of the impact on clinical outcomes and patient preferences. Respir Med. 2015;109(11):1430–8.CrossRefPubMed
21.
Ciciliani A-M, Wachtel H, Langguth P. Comparing Respimat® Soft Mist™ inhaler and DPI aerosol deposition by combined in vitro measurements and CFD simulations. Presented at: Respiratory Drug Delivery 2014; 4-8 May 2014; Fajardo, Puerto Rico.
22.
Keating GM. Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs. 2012;72:273–300.CrossRefPubMed
23.
Anzueto A, Wise R, Pledger G, Calverley P, Dusser D, Cotton D, et al. The Tiotropium Safety and Performance in Respimat (TIOSPIR) trial: bronchodilator efficacy in a spirometry substudy [abstract]. Chest. 2013;144:4. Meeting Abstracts:1027A.CrossRef
24.
Anzueto A, Wise R, Calverley P, Dusser D, Tang W, Metzdorf N, et al. The Tiotropium Safety and Performance in Respimat® (TIOSPIR®) Trial: Spirometry Outcomes. Respir Res. 2015;16:107.CrossRefPubMedPubMedCentral
25.
Bouloukaki I, Giannadaki K, Merigkis C, Michelakis S, Mauroudi E, Moniaki V, et al. Tiotropium Respimat versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD [abstract]. Eur Respir J. 2014;44 Suppl 58:P3280.
26.
Caillaud D, Le Merre C, Martinat Y, Aguilaniu B, Pavia D. A dose-ranging study of tiotropium delivered via Respimat Soft Mist Inhaler or HandiHaler in COPD patients. Int J Chron Obstruct Pulmon Dis. 2007;2:559–65.PubMedPubMedCentral
27.
Calverley P, Anzueto A, Dahl R, Meuller A, Fowler A, Metzdorf N, et al. Tiotropium Safety and Performance In Respimat® (tiospir™): safety and efficacy in patients with tiotropium Handihaler® use at baseline [abstract]. Thorax. 2014;69 Suppl 2:A192 (P262).
28.
Dahl R, Schmidt H, Könen-Bergmann M, Metzdorf N. Mixed treatment analysis comparing tiotropium HandiHaler® and Respimat® [abstract]. Eur Respir J. 2014;44 Suppl 58:925.
29.
Dahl R, Calverley P, Anzueto A. Safety and efficacy of tiotropium in patients switching from HandiHaler® to Respimat® in the TIOSPIR® trial. Submitted manuscript. BMJ Open. 2015;5(12):e009015.CrossRefPubMedPubMedCentral
30.
Halpin DM, Dahl R, Hallmann C, Mueller A, Tashkin D. Tiotropium HandiHaler(®) and Respimat(®) in COPD: a pooled safety analysis. Int J Chron Obstruct Pulmon Dis. 2015;10:239–59.PubMedPubMedCentral
31.
Hohlfeld JM, Sharma A, van Noord JA, Cornelissen PJ, Derom E, Towse L, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54:405–14.CrossRefPubMed
32.
Hohlfeld JM, Furtwaengler A, Konen-Bergmann M, Wallenstein G, Walter B, Bateman ED. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials. Int J Clin Pract. 2015;69:72–80.CrossRefPubMed
33.
Ichinose M, Fujimoto T, Fukuchi Y. Tiotropium 5microg via Respimat and 18microg via HandiHaler; efficacy and safety in Japanese COPD patients. Respir Med. 2010;104:228–36.CrossRefPubMed
34.
Tashkin D, Jones P, Leonard T, Liu D, Metzdorf N, Zubeck V, Wise R. Tiotropium delivered via HandiHaler or Respimat: improvement in health-related quality of life in patients with chronic obstructive pulmonary disease [abstract]. Chest Journal. 2014;146(4_MeetingAbstracts):49A.
35.
Tashkin D, Metzdorf N, Hallmann C, Konen-Bergmann M, Kupas K, Dalby R. Safety of tiotropium in renally impaired patients [abstract]. Eur Respir J. 2014;44 Suppl 58:923.
36.
Tashkin D, Kowey PR, Fowler A, Metzdorf N, Dewberry H, Mueller A, et al. Cardiac safety of tiotropium in patients with cardiac events: a retrospective, combined analysis of the UPLIFT® and TIOSPIR™ trials [abstract]. Am J Respir Crit Care Med. 2015;191:A5770.
37.
van Noord JA, Cornelissen PJ, Aumann JL, Platz J, Mueller A, Fogarty C. The efficacy of tiotropium administered via Respimat Soft Mist Inhaler or HandiHaler in COPD patients. Respir Med. 2009;103:22–9.CrossRefPubMed
38.
Verhamme K, van Blijderveen N, Romio S, Stricker B, Brusselle G, Sturkenboom M. Chronic kidney disease as effect modifier in the association between the use of tiotropium Respimat and mortality [abstract]. Eur Respir J. 2013;42 Suppl 57:4632.
39.
Verhamme KM, Afonso A, Romio S, Stricker BC, Brusselle GG, Sturkenboom MC. Use of tiotropium Respimat Soft Mist Inhaler versus HandiHaler and mortality in patients with COPD. Eur Respir J. 2013;42:606–15.CrossRefPubMed
40.
Wise R, Calverley P, Dahl R, Dusser D, Metzdorf N, Mueller A, et al. Tiotropium safety and performance in respimat® (tiospir™): safety and efficacy in patients naïve to treatment with anticholinergics [abstract]. Thorax. 2014;69 Suppl 2:A192 (P261).
41.
Wise R, Fowler A, Metzdorf N, Dewberry H, Mueller A, Kowey PR. Safety of tiotropium in patients with cardiac events in the TIOSPIR® trial. Presented at: European Respiratory Society International Congress; September 26-30, 2015; 26 September 2015.
42.
Wise R, Kowey PR, Austen G, Lawton A, Mueller A, Metzdorf N, et al. Investigator-reported versus adjudicated cause of death in the TIOSPIR® trial. Presented at: European Respiratory Society International Congress; September 26-30, 2015; 26 September 2015.
43.
Wise RA, Anzueto A, Calverley P, Dahl R, Dusser D, Pledger G, et al. The Tiotropium Safety and Performance in Respimat Trial (TIOSPIR), a large scale, randomized, controlled, parallel-group trial-design and rationale. Respir Res. 2013;14:40.CrossRefPubMedPubMedCentral
44.
Bouloukaki I, Tzanakis N, Mermigkis C, Giannadaki K, Moniaki V, Mauroudi E, et al. Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD. Sleep Breath. 2015;20(2):605–12.CrossRefPubMed
45.
Beasley R. Tiotropium Respimat increases the risk of mortality: pro. Eur Respir J. 2013;42:584–9.CrossRefPubMed
46.
Singh S, Loke YK, Enright PL, Furberg CD. 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.CrossRefPubMedPubMedCentral
47.
Durham MC. Tiotropium (Spiriva): a once-daily inhaled anticholinergic medication for chronic obstructive pulmonary disease. Proc (Bayl Univ Med Cent). 2004;17:366–73.
48.
Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369:1491–501.CrossRefPubMed
49.
Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;7:CD009285.
50.
Kaplan A. Effect of tiotropium on quality of life in COPD: a systematic review. Prim Care Respir J. 2010;19:315–25.CrossRefPubMed
51.
Verhamme KMC, Afonso AS, Romio S, Stricker BC, Brusselle GG, Sturkenboom MC. Patient characteristics at first time use of tiotropium Handihaler vs tiotropium Respimat: is there a potential of channelling? [abstract]. Am J Respir Crit Care Med. 2012;185:A2924.
52.
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;69:598–9.CrossRefPubMed
53.
Dekhuijzen PN, Vincken W, Virchow JC, Roche N, Agusti A, Lavorini F, et al. Prescription of inhalers in asthma and COPD: towards a rational, rapid and effective approach. Respir Med. 2013;107:1817–21.CrossRefPubMed
54.
Vincken W, Dekhuijzen PR, Barnes P. ADMIT Group. The ADMIT series - Issues in inhalation therapy. 4) How to choose inhaler devices for the treatment of COPD. Prim Care Respir J. 2010;19:10–20.CrossRefPubMed
55.
Borel JC, Pepin JL, Pison C, Vesin A, Gonzalez-Bermejo J, Court-Fortune I, et al. Long-term adherence with non-invasive ventilation improves prognosis in obese COPD patients. Respirology. 2014;19:857–65.
56.
Hodder R, Price D. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler. Int J Chron Obstruct Pulmon Dis. 2009;4:381–90.CrossRefPubMedPubMedCentral
57.
Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011;105:930–8.CrossRefPubMed
58.
Freytag F, Rau-Berger H, Glaab T, Wolf K. Respimat® Soft Mist™ inhaler preferred to Diskus by patients with COPD and/or asthma [abstract]. Am J Respir Crit Care Med. 2007;175:A639.
59.
60.
Schurmann W, Schmidtmann S, Moroni P, Massey D, Qidan M. Respimat Soft Mist inhaler versus hydrofluoroalkane metered dose inhaler: patient preference and satisfaction. Treat Respir Med. 2005;4:53–61.CrossRefPubMed
61.
62.
Asakura Y, Nishimura N, Maezawa K, Terajima T, Kizu J, Chohnabayashi N. 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;26:41–5.CrossRefPubMed
63.
Hanada S, Wada S, Ohno T, Sawaguchi H, Muraki M, Tohda Y. Questionnaire on switching from the tiotropium HandiHaler to the Respimat inhaler in patients with chronic obstructive pulmonary disease: changes in handling and preferences immediately and several years after the switch. Int J Chron Obstruct Pulmon Dis. 2015;10:69–77.PubMedPubMedCentral
64.
Nishimura N, Asakura Y, Junta T, Suda R, Yamao S, Tomishima Y, et al. Therapeutic effect of switching tiotropium HandiHaler to Respimat Soft Mist™ inhaler in the patients with COPD: the difference of adverse events and adherence to manipulations between inhaler devices [abstract]. Am J Respir Crit Care Med. 2014;189:A1604.
65.
Suzuki S, Sagara H, Tanaka A, Yamaguchi M, Ohta S, Homma T, et al. Effect of switching administration of tiotropium, HandiHaler to Respimat Soft Mist Inhaler in COPD patients: focus on physical characteristics and background of COPD patients before changing inhaler devices. Am J Respir Crit Care Med. 2014;189:A6004.
66.
Trotta F, Da Cas R, Rajevic M, Rossi M, Traversa G. Risk factors influencing the prescription of tiotropium Respimat formulation: a population-based cohort study. BMJ Open. 2015;5:e006619.CrossRefPubMedPubMedCentral
Metadata
Title
A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?
Authors
Ronald Dahl
Alan Kaplan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2016
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-016-0291-4

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