Drugs

, Volume 66, Issue 11, pp 1475–1483 | Cite as

Beclometasone Dipropionate/Formoterol

In an HFA-Propelled Pressurised Metered-Dose Inhaler
Adis Drug Profile

Abstract

  • ▴ A hydrofluoroalkane (HFA)-propelled pressurised metered-dose inhaler (pMDI) has been developed (using Modulite® technology) for a new fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/formoterol) 100μg/6μg. Each actuation of the BDP/formoterol HFA pMDI 100μg/6μg delivers 86.4μg of BDP and 5μg of formoterol.

  • ▴ BDP/formoterol HFA pMDI was associated with significantly higher morning peak expiratory flow (PEF) values than BDP administered alone via a chlorofluorocarbon (CFC) pMDI (including when BDP was administered at a higher dosage) in well designed trials in adults with mild to moderate or moderate to severe asthma.

  • ▴ In terms of morning PEF values, BDP/formoterol HFA pMDI was noninferior to BDP plus formoterol administered via separate inhalers in well designed trials in adults with moderate to severe asthma.

  • ▴ BDP/formoterol HFA pMDI was noninferior to fixed-combination budesonide/formoterol (the daily dosage of BDP was half that of budesonide) in terms of lung function, asthma symptoms and use of rescue medications in adults with moderate to severe asthma. BDP/formoterol HFA pMDI was also noninferior to, and had a faster onset of bronchodilation than, fixed-combination fluticasone propionate/salmeterol.

  • ▴ BDP/formoterol 200μg/12μg per day or 400μg/ 24μg per day administered by the HFA pMDI was generally well tolerated. Moreover, a single high dose of BDP/formoterol (1000μg/60μg) was generally well tolerated in patients with asthma.

Keywords

Budesonide Severe Asthma Fluticasone Propionate Formoterol Beclometasone 

References

  1. 1.
    Global Initiative for Asthma. Global strategy for asthma management and prevention [online]. Available from URL: http://www.ginasthma.org [Accessed 2005 Oct 17]
  2. 2.
    British Thoracic Society. British guideline on the management of asthma: a national clinical guideline [online]. Available from URL: http://www.sign.ac.uk/pdf/sign63.pdf [Accessed 2005 Jun 15]
  3. 3.
    National Institutes of Health. Pharmacologic therapy: the medications. In: Guidelines for the diagnosis and management of asthma [NIH Publication No. 97-4051]: Bethesda (MD), 1997: 59-79Google Scholar
  4. 4.
    Roche N, Morel H, Martel P, et al. Clinical practice guidelines: medical follow-up of patients with asthma-adults and adolescents. Respir Med 2005; 99(7): 793–815PubMedCrossRefGoogle Scholar
  5. 5.
    Mitchell C, Jenkins C, Scicchitano R, et al. Formoterol (Foradil) and medium-high doses of inhaled corticosteroids are more effective than high doses of corticosteroids in moderate-to-severe asthma. Pulm Pharmacol Ther 2003; 16: 299–306PubMedCrossRefGoogle Scholar
  6. 6.
    Bouros D, Bachlitzanakis N, Kottakis J, et al. Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma. Eur Respir J 1999; 14: 627–32PubMedCrossRefGoogle Scholar
  7. 7.
    Bousquet J. Introduction. Modulite®: simplifying the changeover. Respir Med 2002 Aug; 96 Suppl. D: S1–2PubMedCrossRefGoogle Scholar
  8. 8.
    Chiesi Farmaceutici SpA. Modulite®: the value of Chiesi’s technology in the treatment of asthma and COPD [online]. Available from URL: http://www.chiesigroup.com [Accessed 2006 May 25]
  9. 9.
    Poli G, Acerbi D, Brand P, et al. Lung deposition of formoterol HFA in healthy volunteers, asthmatic and COPD patients [abstract No. P2077 plus poster]. Eur Respir J 2005; 26 (Suppl. 49): 314Google Scholar
  10. 10.
    Lewis D, Brambilla G, Church T, et al. BDP and formoterol association within a combination HFA solution MDI. Respiratory Drug Delivery X 2006; 3: 939–42Google Scholar
  11. 11.
    Data on file. Chiesi Farmaceutici, 2005Google Scholar
  12. 12.
    Ganderton D, Lewis D, Davies R, et al. Modulite: a means of designing the aerosols generated by pressurized metered dose inhalers. Respir Med 2002; 96 (Supl D): S3–8PubMedCrossRefGoogle Scholar
  13. 13.
    Acerbi D, Brambilla G, Kottakis I. Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology. Pulm Pharmacol Ther 2006. Epublication ahead of print: doi:10.1016/j.pupt.2006.05.005Google Scholar
  14. 14.
    Woodcock A, Acerbi D, Poli G. Modulite technology: pharmacodynamic and pharmacokinetic implications. Respir Med 2002; 96 (Suppl D): S9–15PubMedCrossRefGoogle Scholar
  15. 15.
    Brambilla G, Gaderton D, Garzia R, et al. Modulation of aerosol clouds produced by pressurised inhalation aerosols. Int J Pharm 1999; 186: 53–61PubMedCrossRefGoogle Scholar
  16. 16.
    Lewis DA, Ganderton D, Meakin BJ, et al. Theory and practice with solution systems. Respiratory Drug Delivery IX 2004; 1: 109–16Google Scholar
  17. 17.
    Nelson HS, Chapman KR, Pyke SD, et al. Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers. J Allergy Clin Immunol 2003; 112(1): 29–36PubMedCrossRefGoogle Scholar
  18. 18.
    van Schayck CP, Donnell D. The efficacy and safety of QVAR (hydrofluoroalkane-beclometasone dipropionate extrafine aerosol) in asthma (part 1): an update of clinical experience in adults. Int J Clin Pract 2004; 58(7): 678–88PubMedCrossRefGoogle Scholar
  19. 19.
    Rigamonti E, Kottakis I, Pelc M, et al. Comparison of a new HFA134a-formulated extra-fine beclometasone dipropionate pMDI with a standard CFC-formulated BDP pMDI in adults with moderate persistent asthma [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  20. 20.
    Poli G, Acerbi D, Nollevaux F. Pharmacokinetics and pharmacodynamics of a new beclomethasone dipropionate and formoterol CFC-free fixed combination in healthy volunteers [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  21. 21.
    Chung KF, Adcock IM. Combination therapy of long-acting beta-2-adrenoceptor agonists and corticosteroids for asthma. Treat Respir Med 2004; 3(5): 279–89PubMedCrossRefGoogle Scholar
  22. 22.
    Derom E, Pauwels RA. Pharmacokinetic and pharmacodynamic properties of inhaled beclometasone dipropionate delivered via hydrofluoroalkane-containing devices. Clin Pharmacokinet 2005; 44(8): 815–36PubMedCrossRefGoogle Scholar
  23. 23.
    Biggadike K, Uings I, Farrow SN. Designing corticosteroid drugs for pulmonary selectivity. Proc Am Thorac Soc 2004; 1: 352–5PubMedCrossRefGoogle Scholar
  24. 24.
    Cheer SM, Scott LJ. Formoterol: a review of its use in chronic obstructive pulmonary disease. Am J Respir Med 2002; 1(4): 285–300PubMedCrossRefGoogle Scholar
  25. 25.
    Lötvall J. Pharmacological similarities and differences between β2-agonists. Respir Med 2001; 95 Suppl. B: S7–11PubMedCrossRefGoogle Scholar
  26. 26.
    Palmqvist M, Persson G, Lazer L, et al. Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency. Eur Respir J 1997; 10: 2484–9PubMedCrossRefGoogle Scholar
  27. 27.
    Rabe KF, Jorres R, Nowak D, et al. Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993; 147: 1436–41PubMedGoogle Scholar
  28. 28.
    Profita M, Gagliardo R, Di Giorgi R, et al. Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics. Allergy 2005; 60(3): 323–9PubMedCrossRefGoogle Scholar
  29. 29.
    Eickelberg O, Roth M, Lorx R, et al. Ligand-independent activation of the glucocorticoid receptor by β2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 1999; 274(2): 1005–10PubMedCrossRefGoogle Scholar
  30. 30.
    Pang L, Knox AJ. Synergistic inhibition of β2-agonists and corticosteroids on tumor necrosis factor-a-induced interleukin-8 release from cultured human airway smooth-muscle cells. Am J Resp Cell Mol Biol 2000; 23: 79–85Google Scholar
  31. 31.
    Piccinno A, Borrill Z, Poli G, et al. Tolerability of high cumulative doses of a new fixed combination of beclomethasone dipropionate/formoterol in asthmatic patients. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  32. 32.
    Daley-Yates PT, Price AC, Sisson JR, et al. Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001; 51: 400–9PubMedCrossRefGoogle Scholar
  33. 33.
    Bonnet-Gonod F, Kottakis I, Ballabio M, et al. Superior efficacy of a low daily dose of a new fixed combination of beclometasone dipropionate/formoterol pMDI compared to an increased daily dose of BDP in moderate persistent asthma: a 3 month clinical study [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  34. 34.
    Paggiaro P, Papi A, Feschenko YI, et al. Efficacy and safety of the new beclomethasone dipropionate/formoterol combination vs. fluticasone propionate/salmeterol pMDIs in moderate to severe persistent asthma [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  35. 35.
    Papi A, Paggiaro P, Zarkovic J, et al. Efficacy and safety of the new beclomethasone dipropionate/formoterol combination (HFA MDI) vs. budesonide/formoterol (DPI) in moderate to severe persistent asthma [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  36. 36.
    Bonnet-Gonod F, Kottakis I, Hofman T, et al. Beclometasone dipropionate/formoterol in a single inhaler improves lung function and clinically meaningful outcomes in moderate to severe asthma [abstract]. 16th Annual Congress of the European Respiratory Society; 2006 Sep 2–6; MunichGoogle Scholar
  37. 37.
    Ankerst J, Persson G, Weibull E. Tolerability of a high dose of budesonide/formoterol in a single inhaler in patients with asthma. Pulm Pharmacol Ther 2003; 16: 147–51PubMedCrossRefGoogle Scholar
  38. 38.
    Chiesi Farmaceutici SpA. Wortlaut der fur das Behaltnis (Druckbehaltnis) vogesehenen Angaben: SmPC Foster 100/6 Mikrogramm. Italy: Chiesi Farmaceutici SpA, July 2006Google Scholar
  39. 39.
    Bundesinstitut fur Arzneimittel und Medizinprodukte. Approval letter for Kantos 100/6 Mikrogramm Druckgasinhalation and Foster 100/6 Mikrogramm Druckgasinhalation. 2006 Jul 14Google Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

Personalised recommendations