- Medicines and Healthcare products Regulatory Agency
- 10 November 2010
- Last updated:
- 11 December 2014, see all updates
- Therapeutic area:
- Respiratory disease and allergy
Safety studies of Spiriva Respimat▼
This article has been superseded. See updated article published in February 2015 for latest advice
Article date: November 2010
Tiotropium is a long-acting muscarinic receptor antagonist that is licensed as a prescription-only medicine for maintenance bronchodilator treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD). Two formulations are available as the brand name Spiriva: a capsule containing 18 micrograms tiotropium delivered via a HandiHaler taken once daily and a soft-mist Respimat inhaler that delivers 2∙5 micrograms tiotropium per actuation taken as two puffs once a day at the same time of the day.
Recent safety analyses for Spiriva Respimat▼
MHRA has previously highlighted the conflicting findings of a number of recent studies on the safety of inhaled anticholinergic drugs. Although some published studies have suggested an increased risk of cardiovascular death, myocardial infarction, or stroke associated with use of these medicines, a large 4-year placebo-controlled randomised double-blind trial concluded that tiotropium delivered via HandiHaler was associated with a non-significantly decreased risk of all-cause mortality, myocardial infarction, or stroke compared with placebo.
A recently completed safety study that compared Spiriva Respimat▼ with placebo in patients with COPD found that lung function, COPD exacerbations, and quality of life were improved by 5 micrograms Respimat, but a numerical increase was seen in all-cause mortality compared with placebo. A retrospective pooled analysis of three 1-year and one 6-month placebo-controlled trials with Spiriva Respimat including 6096 patients found a non-significant numerical increase in all-cause mortality in patients treated with Spiriva Respimat: 68 patients using Spiriva Respimat died (incidence rate [IR] 2.64 cases per 100 patient-years) compared with 51 deaths in patients on placebo (IR 1.98 cases per 100 patient-years)—rate ratio 1.33 (95% CI 0.93–1.92) for the planned treatment period. In a posthoc analysis of different patient subgroups, a significant excess in mortality was observed in patients with known cardiac rhythm disorders. By contrast, pooled analysis of studies longer than 4 weeks that included 17 014 patients assigned to Spiriva HandiHaler or placebo showed a rate ratio for all-cause mortality of 0.85 (95% CI 0.75–0.97).
There were differences between the Respimat and HandiHaler study populations at baseline, including smoking status, gender, and disease severity, and the causes of death varied across studies. The underlying reasons for the apparent difference in the risk of all-cause mortality between the HandiHaler and Respimat devices are unclear, and may be a chance finding. Further studies are ongoing to investigate these differences.
Information and advice for healthcare professionals:
- recent analyses found that Spiriva Respimat was associated with a non-significant increase in all-cause mortality compared with placebo; by contrast, Spiriva HandiHaler was associated with a decrease in all-cause mortality compared with placebo - the underlying reasons for the apparent difference are unclear, and may be a chance finding; further studies are ongoing
- Spiriva Respimat should be used with caution in patients with known cardiac rhythm disorders
- patients with COPD who use tiotropium should be reminded not to exceed the recommended once-daily dose of:
- Spiriva HandiHaler 18-microgram capsule, or
- 2 puffs Spiriva Respimat 2.5 micrograms
Please remember to report suspected adverse reactions to Spiriva HandiHaler or Spiriva Respimat on a Yellow Card at www.yellowcard.gov.uk.
Article citation: Drug Safety Update Nov 2011 vol 4, issue 4: H2.
Published: 10 November 2010
Updated: 11 December 2014
- Published to website
- First published.
Therapeutic area: Respiratory disease and allergy