title: Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data.
abstract: BACKGROUND
  Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents.
  
  
  METHODS
  We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 μg, placebo (both delivered via the Breezhaler device), or tiotropium 18 μg (delivered via the HandiHaler device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated.
  
  
  RESULTS
  The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data.
  
  
  CONCLUSIONS
  The overall safety profile of glycopyrronium was similar to its comparators indicating no increase in the overall risk for any of the investigated safety end points.
authors: Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
authors: Anthony D
authors: AD
authors: D'Urzo
authors: Clinical Research Institute of Southern Oregon, PC, Medford, USA.
authors: Edward M
authors: EM
authors: Kerwin
authors: Asthma and Airway Centre, University Health Network, Toronto Western Hospital, Toronto, ON, Canada.
authors: Kenneth R
authors: KR
authors: Chapman
authors: Respiratory Division, University of Leuven, Leuven, Belgium.
authors: Marc
authors: M
authors: Decramer
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Robert
authors: R
authors: DiGiovanni
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors: Peter
authors: P
authors: D'Andrea
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors: Huilin
authors: H
authors: Hu
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Pankaj
authors: P
authors: Goyal
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors: Pablo
authors: P
authors: Altman
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009330:Nebulizers and Vaporizers; D061214:Patient Safety; D011358:Product Surveillance, Postmarketing; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate
keywords: COPD; drug safety; glycopyrronium; post-marketing surveillance