Safety and tolerability of inhalational anticholinergics in COPD

Amir Sharafkhaneh, Hashir Majid, Nicholas J Gross, Amir Sharafkhaneh, Hashir Majid, Nicholas J Gross

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. With the significant toll of the disease, more resources have been invested in developing new treatment modalities. Among these medications, inhalational anticholinergics are widely used for the management of stable COPD. The newer agents, with longer half-lives and better safety profiles, have emerged and helped to improve management of COPD patients. The available data from randomized clinical trials support use of these agents. Multiple randomized clinical trials show safety and efficacy of the newer long-acting inhaled anticholinergics, including tiotropium and aclidinium. A recent meta-analysis of tiotropium delivered with Respimat(®) raised some safety concerns. A large trial, comparing different doses and delivery methods of inhaled tiotropium, is ongoing to determine the effect on mortality. As clinical trials may not comprehensively represent the entire COPD population, caution should be exercised when these agents are used in higher-risk populations, like individuals with cardiac arrhythmias or urinary obstruction. In this publication, we review the safety of inhalational anticholinergics.

Keywords: aclidinium; arrhythmia; cardiovascular side effects; stroke; tiotropium.

References

    1. Minino AM, Xu J, Kochanek KD.Deaths: Preliminary Data for 2008 Atlanta: Centers for Disease Control and Prevention; 2010Available from: Accessed August 30, 2012
    1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance – United States, 1971–2000. MMWR Surveill Summ. 2002;51(6):1–16.
    1. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176:532–555.
    1. Cooper CB. The connection between chronic obstructive pulmonary disease symptoms and hyperinflation and its impact on exercise and function. Am J Med. 2006;119(10 Suppl 1):21–31.
    1. Celli BR, MacNee W, ATS/ERS Task Force Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ ERS position paper. Eur Respir J. 2004;23(6):932–946.
    1. Anthonisen NR, Connett JE, Kiley J P, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA. 1994;272(19):1497–1505.
    1. Rabe KF, Beghé B, Luppi F, Fabbri LM. Update in chronic obstructive pulmonary disease 2006. Am J Respir Crit Care Med. 2007;175(12):1222–1232.
    1. Moulton BC, Fryer AD. Muscarinic receptor antagonists, from folklore to pharmacology; finding drugs that actually work in asthma and COPD. Br J Pharmacol. 2001;163(1):44–52.
    1. Restrepo RD. Use of inhaled anticholinergic agents in obstructive airway disease. Respir Care. 2007;52(1):833–851.
    1. Gross NJ. Anticholinergic agents in asthma and COPD. Eur J Pharmacol. 2006;533(1–3):36–39.
    1. Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T. The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests. Am J Respir Crit Care Med. 2000;161(6):1897–1901.
    1. Cazzola M, Di Perna F, Califano C, Vinciguerra A, D’Amato M. Incremental benefit of adding oxitropium bromide to formoterol in patients with stable COPD. Pulm Pharmacol Ther. 1999;12(4):267–271.
    1. Tashkin DP, Celli B, Senn S, et al. UPLIFT Study Investigators A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–1554.
    1. Niewoehner DE, Rice K, Cote C, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005;143(5):317–326.
    1. O’Donnell DE, Flüge T, Gerken F, et al. Effects of tiotropium on lung hyperinfation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–840.
    1. Sims MW, Panettieri RA., Jr Profile of aclidinium bromide in the treatment of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2011;6:457–466.
    1. Food and Drug Administration (FDA) NDA 202-450: aclidinium bromide for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema Paper presented at: Pulmonary Allergy Drugs Advisory Committee Meeting; 2012 Feb 23Silver Spring MD Available from: Accessed August 30, 2012
    1. 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.
    1. Boehringer Ingelheim Pharmaceuticals Comparison of tiotropium in the HandhiHaler versus the Respimat in chronic obstructive pulmonary disease ClinicalTrialsgov [website on the Internet] Bethesda, MD: US National Institutes of Health; 2011[updated October 30, 2012. Available from: . NLM identifier: NCT01126437Accessed August 30, 2012
    1. McLachlan AJ, Pont LG. Drug metabolism in older people – a key consideration in achieving optimal outcomes with medicines. J Gerontol A Biol Sci Med Sci. 2012;67(2):175–180.
    1. McLachlan AJ, Hilmer SN, Le Couteur DG. Variability in response to medicines in older people: phenotypic and genotypic factors. Clin Pharmacol Ther. 2009;85(4):431–433.
    1. Nicolson TJ, Mellor HR, Roberts RR. Gender differences in drug toxicity. Trends Pharmacol Sci. 2010;31(3):108–114.
    1. Montastruc JL, Lapeyre-Mestre M, Bagheri H, Fooladi A. Gender differences in adverse drug reactions: analysis of spontaneous reports to a Regional Pharmacovigilance Centre in France. Fundam Clin Pharmacol. 2002;16(5):343–346.
    1. Vestbo J, Soriano JB, Anderson JA, Calverley P, Pauwels R, Jones P, TRISTAN Study Group Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD. Respir Med. 2004;98(11):1045–1050.
    1. Phan VH, Moore MM, McLachlan AJ, Piquette-Miller M, Xu H, Clarke SJ. Ethnic differences in drug metabolism and toxicity from chemotherapy. Expert Opin Drug Metab Toxicol. 2009;5(3):243–257.
    1. Criner GJ, Sharafkhaneh A, Player R, et al. Efficacy of tiotropium inhalation powder in african-american patients with chronic obstructive pulmonary disease. COPD. 2008;5(1):35–41.
    1. Rice KL, Leimer I, Kesten S, Niewoehner DE. Responses to tiotropium in African-American and Caucasian patients with chronic obstructive pulmonary disease. Transl Res. 2008;152(2):88–94.
    1. Wu Q, Li G, Lei WI, Zhou X. The efficacy and safety of tiotropium in Chinese patients with stable chronic obstructive pulmonary disease: a meta-analysis. Respirology. 2009;14(5):666–674.
    1. Boehringer Ingelheim Pharmaceutical Spiriva Handihaler 2001Accessed August 30, 2012
    1. Anthonisen NR, Connett JE, Enright PL, Manfreda J, Lung Health Study Research Group Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med. 2002;166(3):333–339.
    1. Kesten S, Celli B, Decramer M, Leimer I, Tashkin D. Tiotropium HandiHaler in the treatment of COPD: a safety review. Int J Chron Obstruct Pulmon Dis. 2009;4:397–409.
    1. 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):1439–1450.
    1. Michele TM, Pinheiro S, Iyasu S. The safety of tiotropium – the FDA’s conclusions. N Engl J Med. 2010;363(12):1097–1099.
    1. 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(1):22–29.
    1. Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med. 2008;149(6):380–390.
    1. Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest. 2010;137(1):13–19.
    1. Kesten S, Jara M, Wentworth C, Lanes S. Pooled clinical trial analysis of tiotropium safety. Chest. 2006;130(6):1695–1703.
    1. Oba Y, Zaza T, Thameem DM. Safety, tolerability and risk benefit analysis of tiotropium in COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(4):575–584.
    1. Kesten S, Jara M, Wentworth C, Lanes S. Pooled clinical trial analysis of tiotropium safety. Chest. 2006;130(6):1695–1703.
    1. Spiriva Handihaler® Capsule (Tiotropium Bromide Inhalational Powder) [package insert] Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; 2004.
    1. Lust K, Livingstone I. Nebulizer-induced anisocoria. Ann Intern Med. 1998;128(4):327.
    1. Wehbe E, Antoun SA, Moussa J, Nassif I. Transient anisocoria caused by aerosolized ipratropium bromide exposure from an ill-fitting face mask. J Neuroophthalmol. 2008;28(3):236–237.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere