Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease: a population-based study.
ABSTRACT Inhaled anticholinergic medications (IACs) are widely used treatments for chronic obstructive pulmonary disease (COPD). The systemic anticholinergic effects of IAC therapy have not been extensively studied. This study sought to determine the risk of acute urinary retention (AUR) in seniors with COPD using IACs.
A nested case-control study of individuals with COPD aged 66 years or older was conducted from April 1, 2003, to March 31, 2009, using population-based linked databases from Ontario, Canada. A hospitalization, same-day surgery, or emergency department visit for AUR identified cases, which were matched with up to 5 controls. Exposure to IACs was determined using a comprehensive drug benefits database. Conditional logistic regression analysis was conducted to determine the association between IAC use and AUR.
Of 565,073 individuals with COPD, 9432 men and 1806 women developed AUR. Men who just initiated a regimen of IACs were at increased risk for AUR compared with nonusers (adjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.20-1.68). In men with evidence of benign prostatic hyperplasia, the risk was increased further (OR, 1.81; 95% CI, 1.46-2.24). Men using both short- and long-acting IACs had a significantly higher risk of AUR compared with monotherapy users (OR, 1.84; 95% CI, 1.25-2.71) or nonusers (2.69; 1.93-3.76).
Use of short- and long-acting IACs is associated with an increased risk of AUR in men with COPD. Men receiving concurrent treatment with both short- and long-acting IACs and those with evidence of benign prostatic hyperplasia are at highest risk.
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ABSTRACT: Tiotropium is a long-acting inhaled anticholinergic agent that is widely used in the treatment of chronic obstructive pulmonary disease (COPD). It was initially launched as the tiotropium HandiHaler formulation, but this was followed by a newer version based on a potentially more efficient drug delivery device, known as Respimat. This Respimat formulation is available worldwide but has not yet succeeded in gaining regulatory approval in the USA. In the past few years, the adverse effects profile of tiotropium has come under close scrutiny owing to concerns about the possibility of urinary and cardiovascular adverse effects. These concerns appeared to have been alleviated following the publication of data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, which was a large trial of 4 years' duration. This trial did not show any excess myocardial infarction, renal or urinary adverse events with tiotropium compared with placebo. However, the risk of urinary retention has been in the spotlight again following publication of two observational studies reporting a significantly increased risk of urinary retention in men recently started on inhaled anticholinergics, especially when prostatic hyperplasia coexists. More recently, a meta-analysis of mortality data for the tiotropium Respimat formulation raised the possibility of an increased risk of death, including death from cardiovascular causes. It is unclear if the more efficient drug delivery offered by the Respimat device is hitting a different part of the dose-toxicity curve. In the absence of any evidence of superior clinical efficacy with tiotropium Respimat compared with tiotropium HandiHaler, some experts have argued that there is no compelling reason to choose the Respimat formulation given the new uncertainties about its safety profile.Therapeutic advances in drug safety. 06/2012; 3(3):123-31.
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance. These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC) bromide/vilanterol trifenatate (VI), aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany). This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 μg and 62.5/25 μg in patients with COPD. Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function. Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted.International Journal of COPD 01/2014; 9:687-695.
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ABSTRACT: Inhaled anticholinergics (ipratropium bromide and tiotropium bromide) are widely used as maintenance treatment in chronic obstructive pulmonary disease. Previous studies have reported on their cardiovascular effects but relatively little is known about their effects on the bladder. Acute urinary retention is a medical emergency which can be associated with serious complications. Our objective was to evaluate the existing literature regarding the effects of inhaled anticholinergics on urinary retention among patients with chronic obstructive pulmonary disease. We searched PubMed and the United States Food and Drug Administration (FDA) adverse events database for case reports, observational studies, randomized controlled trials (or meta-analyses of such trials) that reported on the outcome of urinary retention with inhaled anticholinergics (ipratropium or tiotropium). We checked 27 published articles and identified relevant papers including two case reports, three pooled analyses, two observational studies and one randomized controlled trial. Two of the observational studies and a pooled analysis of randomized controlled trials reported a significant increase in the risk of acute urinary retention with inhaled anticholinergics. Older patients with benign prostatic hyperplasia seem to be at the highest risk of this adverse effect which tends to occur soon after treatment initiation. Although all the links in the chain have yet to be fully elucidated, the preponderance of evidence suggests the possibility of a causal relationship between inhaled anticholinergics and urinary retention. Clinicians should carefully balance these and other adverse effects of inhaled anticholinergics against their known symptomatic benefits on exacerbations, after eliciting patient preferences for various outcomes in a shared decision-making context.Therapeutic advances in drug safety. 02/2013; 4(1):19-26.