Skip to main content
SpringerLink
Log in

Indacaterol

A Review of its Use as Maintenance Therapy in Patients with Chronic Obstructive Pulmonary Disease

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Indacaterol inhalation powder (Onbrez® Breezhaler®) is a long-acting, selective β2-adrenoceptor agonist that is indicated for the maintenance bronchodilator treatment of airflow obstruction in adults with chronic obstructive pulmonary disease (COPD). This article reviews the clinical efficacy and tolerability of indacaterol 150 and 300 mg once daily in adults with moderate to severe COPD, as well as reviewing indacaterol’s pharmacological properties and results of a cost-utility analysis.

Indacaterol has a fast onset of action after the first dose and is effective over 24 hours, allowing for once-daily administration. In short-term trials (≤21 days) in patients with COPD, once-daily indacaterol 150 or 300 mg significantly improved lung function, exercise endurance and lung hyperinflation relative to placebo.

In large, longer-term clinical studies (12 weeks to 1 year) in patients with moderate to severe COPD, once-daily indacaterol 150 or 300 μg improved lung function (primary endpoint) significantly more than placebo, and improvements were significantly greater than twice-daily formoterol 12μg or salmeterol 50mg, and noninferior to once-daily tiotropium bromide 18μg (all agents were administered via inhalation). Overall, indacaterol improved dyspnoea, use of rescue medication and general health status significantly more than placebo, salmeterol or tiotropium bromide, and the degree of improvement in these endpoints was similar to or greater than that achieved with formoterol. Improvements were sustained over the long term (1 year), with no evidence of tolerance.

Combination therapy with indacaterol plus tiotropium bromide improved lung function, dyspnoea, rescue medication use and general health status significantly more than tiotropium bromide alone in patients with moderate to severe COPD.

Indacaterol is generally well tolerated when used alone or in combination with tiotropium bromide in patients with COPD and has not been associated with any safety issues. The most common adverse event in clinical trials was COPD worsening, which occurred more commonly with placebo than indacaterol. Indacaterol was not associated with an increased risk of cardiovascular adverse events.

In a cost-utility analysis from a German healthcare payer perspective, oncedaily indacaterol 150 mg was dominant (i.e. more effective with lower total costs) to once-daily tiotropium bromide 18 mg and twice-daily salmeterol 50 μg in the treatment of patients with COPD.

In conclusion, indacaterol provides a valuable option for the maintenance treatment of adults with COPD.

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.

Table I
Table II
COPD
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (revised 2011) [online]. Available from URL: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011Dec30.pdf [Accessed 2012 Feb 7]

  2. European Medicines Agency. Onbrez Breezhaler (indacaterol) 150 μg inhalation powder, hard capsules: summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001114/WC500053732.pdf [Accessed 2012 Jan 9]

  3. Pavkov R, Mueller S, Fiebich K, et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. Curr Med Res Opin 2010 Nov; 26(11): 2527–33

    Article  PubMed  CAS  Google Scholar 

  4. Chapman KR, Fogarty CM, Peckitt C, et al. Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD. Int J Chron Obstruct Pulmon Dis 2011;6: 353–63

    PubMed  Google Scholar 

  5. Moen MD. Indacaterol: in chronic obstructive pulmonary disease. Drugs 2010 Dec 3; 70(17): 2269–80

    Article  PubMed  CAS  Google Scholar 

  6. Battram C, Charlton SJ, Cuenoud B, et al. In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-Diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a novel inhaled gb2 adrenoceptor agonist with a 24-h duration of action. J Pharmacol Exp Ther 2006 May; 317(2): 762–70

    Article  PubMed  CAS  Google Scholar 

  7. Naline E, Trifilieff A, Fairhurst RA, et al. Effect of indacaterol, a novel long-acting b2-agonist, on isolated human bronchi. Eur Respir J 2007 Mar; 29(3): 575–81

    Article  PubMed  CAS  Google Scholar 

  8. Baur F, Beattie D, Beer D, et al. The identification of indacaterol as an ultralong-acting inhaled b2-adrenoceptor agonist. J Med Chem 2010 May; 53(9): 3675–84

    Article  PubMed  CAS  Google Scholar 

  9. Lombardi D, Cuenoud B, Krämer SD. Lipid membrane interactions of indacaterol and salmeterol: do they influence their pharmacological properties? Eur J Pharm Sci 2009 Dec 8; 38(5): 533–47

    Article  PubMed  CAS  Google Scholar 

  10. Rennard S, Bantje T, Centanni S, et al. A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison. Respir Med 2008 Jul; 102(7): 1033–44

    Article  PubMed  Google Scholar 

  11. Bauwens O, Ninane V, Van de Maele B, et al. 24-hour bronchodilator efficacy of single doses of indacaterol in subjects with COPD: comparison with placebo and formoterol. Curr Med Res Opin 2009 Feb; 25(2): 463–70

    Article  PubMed  CAS  Google Scholar 

  12. Beier J, Beeh KM, Brookman L, et al. Bronchodilator effects of indacaterol and formoterol in patients with COPD. Pulm Pharmacol Ther 2009 Dec; 22(6): 492–6

    Article  PubMed  CAS  Google Scholar 

  13. Laforce C, Aumann J, de Teresa Parreno L, et al. Sustained 24-hour efficacy of once daily indacaterol (300 μg) in patients with chronic obstructive pulmonary disease: a randomized, crossover study. Pulm Pharmacol Ther 2011 Feb; 24(1): 162–8

    Article  PubMed  CAS  Google Scholar 

  14. Balint B, Watz H, Amos C, et al. Onset of action of indacaterol in patients with COPD: comparison with salbutamol and salmeterol-fluticasone. Int J Chron Obstruct Pulmon Dis 2010 Sep 7; 5: 311–8

    PubMed  CAS  Google Scholar 

  15. Vogelmeier C, Ramos-Barbon D, Jack D, et al. Indacaterol provides 24-hour bronchodilation in COPD: a placebocontrolled blinded comparison with tiotropium. Respir Res 2010 Oct 5; 11(1): 135

    Article  PubMed  Google Scholar 

  16. Magnussen H, Verkindre C, Jack D, et al. Indacaterol oncedaily is equally effective dosed in the evening or morning in COPD. Respir Med 2010 Sep; 104(12): 1869–76

    Article  PubMed  CAS  Google Scholar 

  17. O’Donnell DE, Casaburi R, Vincken W, et al. Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respir Med 2011 Jul; 105(7): 1030–6

    Article  PubMed  Google Scholar 

  18. Beeh KM, Wagner F, Khindri S, et al. Effect of indacaterol on dynamic lung hyperinflation and breathlessness in hyperinflated patients with COPD. COPD 2011 Oct; 8(5): 340–5

    Article  PubMed  Google Scholar 

  19. Rossi A, Centanni S, Cerveri I, et al. Acute effects of indacaterol on lung hyperinflation in moderate COPD: a comparison with tiotropium. Respir Med 2012; 106(1): 84–90

    Article  PubMed  Google Scholar 

  20. Puente-Maestu L, Villar F, de Miguel J, et al. Clinical relevance of constant power exercise duration changes in COPD. Eur Respir J 2009; 34: 340–5

    Article  PubMed  CAS  Google Scholar 

  21. Renard D, Looby M, Kramer B, et al. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches. Respir Res 2011; 12: 54

    Article  PubMed  CAS  Google Scholar 

  22. Khindri S, Sabo R, Harris S, et al. Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study. BMC Pul Med 2011 May 26; 11 (31)

  23. Worth H, Chung KF, Felser JM, et al. Cardioand cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med 2011 Apr; 105(4): 571–9

    Article  PubMed  Google Scholar 

  24. Donohue JF, Singh D, Kornmann O, et al. Safety of indacaterol in the treatment of patients with COPD. Int J Chron Obstruct Pulm Dis 2011 Sep; 6: 477–92

    Article  CAS  Google Scholar 

  25. Perry S, Woessner R, Kaiser G, et al. Pharmacokinetics of indacaterol after single and multiple inhaled doses [abstract no. A4420]. Am J Respir Crit Care Med 2010; 181. Plus poster presented at the 106th International Conference of the American Thoracic Society; 2010 May 14–19; New Orleans (LA)

  26. Hosoe M, Woessner R, Matsushima S, et al. Efficacy, safety and pharmacokinetics of indacaterol in Caucasian and Japanese patients with chronic obstructive pulmonary disease: a comparison of data from two randomized, placebocontrolled studies. Clin Drug Invest 2011; 31(4): 247–55

    Article  CAS  Google Scholar 

  27. Perry S, Goldsmith P, Vaidyanathan S, et al. No significant clinical drug-drug interaction potential with indacaterol [abstract no P3985 plus poster]. European Respiratory Society Annual Congress; 2011 Sep 24–28; Amsterdam

  28. Korn S, Kerwin E, Atis S, et al. Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study. Respir Med 2011 May; 105(5): 719–26

    Article  PubMed  Google Scholar 

  29. Dahl R, Chung KF, Buhl R, et al. Efficacy of a new oncedaily long-acting inhaled β2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax 2010 Jun; 65(6): 473–9

    Article  PubMed  Google Scholar 

  30. Kornmann O, Dahl R, Centanni S, et al. Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison. Eur Respir J 2011 Feb; 37(2): 273–9

    Article  PubMed  CAS  Google Scholar 

  31. Feldman G, Siler T, Prasad N, et al. Efficacy and safety of indacaterol 150mg once-daily in COPD: a double-blind, randomised, 12-week study. BMC Pulm Med 2010; 10: 11

    Article  PubMed  Google Scholar 

  32. Buhl R, Dunn LJ, Disdier C, et al. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD. Eur Respir J 2011 May; 38(4): 797–803

    Article  PubMed  CAS  Google Scholar 

  33. Donohue JF, Fogarty C, Lötvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med 2010; 182(2): 155–62

    Article  PubMed  CAS  Google Scholar 

  34. Kinoshita M, Lee SH, Hang LW, et al. Efficacy and safety of indacaterol 150 and 300 μg in chronic obstructive pulmonary disease (COPD) patients from six Asian areas including Japan: a 12-week, placebo-controlled study. Respirology 2012 Feb; 17(2): 379–89

    Article  PubMed  Google Scholar 

  35. To Y, Nishimura M, Fukuchi Y, et al. Long-term safety and tolerability of indacaterol versus salmeterol in Japanese COPD patients: a 52-week openlabeled study [abstract no. 240]. Respirology 2011; 16 Suppl. 2: 96

    Google Scholar 

  36. Mahler DA, D’Urzo A, Peckitt C, et al. Combining oncedaily bronchodilators in COPD: indacaterol plus tiotropium versus tiotropium alone [abstract no. A1591 plus poster]. 107th International Conference of the American Thoracic Society; 2011 May 13–18; Denver (CO)

  37. Barnes PJ, Pocock SJ, Magnussen H, et al. Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design. Pulm Pharmacol Ther 2010 Jun; 23(3): 165–71

    Article  PubMed  CAS  Google Scholar 

  38. Chapman KR, Rennard SI, Dogra A, et al. Long-term safety and efficacy of indacaterol, a long-acting β2-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest 2011 Jul; 140(1): 68–75

    Article  PubMed  CAS  Google Scholar 

  39. Bleecker ER, Siler T, Owen R, et al. Bronchodilator efficacy and safety of indacaterol 150 μg once daily in patients with COPD: an analysis of pooled data. Int J Chron Obstruct Pulm Dis 2011; 6: 431–8

    CAS  Google Scholar 

  40. Korn S, Kornmann O, Dunn L, et al. Efficacy of indacaterol is maintained in patients with moderate or less (GOLD I-II) and severe or worse (GOLD III-IV) COPD [abstract P860 plus poster]. European Respiratory Society Annual Congress; 2011 Sep 24–28; Amsterdam

  41. Jones PW, Quirk FH, Bavesystock CM, et al. A selfcomplete measure of health status for chronic airflow limitation. The St George’s Respiratory Questionnaire. Am Rev Respir Dis 1992; 145: 1321–7

    Article  CAS  Google Scholar 

  42. Jones PW, Mahler DA, Gale R, et al. Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respir Med 2011 Jun; 105(6): 892–9

    Article  PubMed  Google Scholar 

  43. Price D, Gray A, Gale R, et al. Cost-utility analysis of indacaterol in Germany: a once-daily maintenance bronchodilator for patients with COPD. Respir Med 2011 Nov; 105(11): 1635–47

    Article  PubMed  Google Scholar 

  44. Oostenbrink JB, Rutten-van Molken MPH, Monz BU, et al. Probabilistic Markov model to assess the cost-effectiveness of bronchodilator therapy in COPD patients in different countries. Value Health 2005; 8(1): 32–46

    Article  PubMed  Google Scholar 

  45. Cazzola M, MacNee W, Martinez FJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 2008; 31: 416–68

    Article  PubMed  CAS  Google Scholar 

  46. Novartis. Arcapt™ Neohaler™ (indacaterol inhalation powder) full prescribing information [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/arcapta.pdf [Accessed 2012 Jan 12]

  47. Chowdhury BA, Seymour SM, Michele TM, et al. The risks and benefits of indacaterol: the FDA’s review. N Engl J Med 2011; 365(124): 2247–9

    Article  PubMed  CAS  Google Scholar 

  48. Cazzola M, Molimard M. The scientific rationale for combining long-acting β2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther 2010; 23(4): 257–67

    Article  PubMed  CAS  Google Scholar 

  49. Cope S, Capkun-Niggli G, Gale R, et al. Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease: a network meta-analysis. Int J Chron Obstruct Pulmon Dis 2011; 6: 329–44

    Article  PubMed  CAS  Google Scholar 

  50. Schneider C, Bothner U, Jick SS, et al. Chronic obstructive pulmonary disease and the risk of cardiovascular diseases. Eur J Epidemiol 2010; 25(4): 253–60

    Article  PubMed  Google Scholar 

  51. Insulander P, Juhlin-Dannfelt A, Freyschuss U, et al. Electrophysiologic effects of salbutamol, a β2-selective agonist. J Cardiovasc Electrophysiol 2004; 15(3): 316–22

    Article  PubMed  Google Scholar 

  52. Toy EL, Beaulieu NU, McHale JM, et al. Treatment of COPD: relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med 2011 Mar; 105(3): 435–41

    Article  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. 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.

Author information

Authors and Affiliations

  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Kate McKeage

Authors
  1. Kate McKeage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kate McKeage.

Additional information

Various sections of the manuscript reviewed by: R. Buhl, Pulmonary Department, Mainz University Hospital, Mainz, Germany; J.F. Donohue, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; K-M. Beeh, Insaf Respiratory Research Institute, Wiesbaden, Germany; M. Cazzola, Unit of Respiratory Clinical Pharmacology, University of Rome ‘Tor Vergata’, Rome, Italy; H. Worth, Medical Department I, Klinikum Fürth, Fürth, Germany.

Data Selection

Sources: Medical literature (including published and unpublished data) on indacaterol was identified by searching databases (including MEDLINE, EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were ‘indacaterol’ and (‘chronic obstructive pulmonary disease’ or ‘pulmonary disease, chronic obstructive’ or ‘chronic obstructive lung disease’). Searches were last updated 7 February 2012.

Selection: Studies in patients with chronic obstructive pulmonary disease who received indacaterol. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Indacaterol, chronic obstructive pulmonary disease, pharmacodynamics, pharmacokinetics, pharmacoeconomics, therapeutic use, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McKeage, K. Indacaterol. Drugs 72, 543–563 (2012). https://doi.org/10.2165/11208490-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11208490-000000000-00000

Keywords

Search

Navigation