Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler)
[01-14-2010] This is a Follow-Up to previous Early Communications issued in 2008 by the U.S. Food and Drug Administration (FDA) describing a potential increase in the risk of stroke, heart attack, or death from a cardiovascular cause related to the use of tiotropium, which is marketed as Spiriva HandiHaler. FDA has now completed its review and believes the available data do not support an association between the use of Spiriva HandiHaler and an increased risk for these serious adverse events.
FDA is advising healthcare professionals to continue to prescribe Spiriva HandiHaler as recommended in the drug label.
Spiriva HandiHaler is a long-acting respiratory medication used for the treatment of chronic obstructive pulmonary disease (COPD). Consumers currently using Spiriva HandiHaler should talk to their healthcare professional if they have any questions or concerns about the use of this medication.
The March 2008 Early Communication described data submitted by the manufacturer of Spiriva HandiHaler that suggested there may be a small excess risk of stroke in patients using tiotropium (the active ingredient in Spiriva HandiHaler) compared to placebo (2 cases of stroke per 1000 treated patients). The Updated Early Communication from October 2008 reported two additional publications that suggested an increased risk of death, heart attack or stroke in patients using tiotropium or drugs that work similarly to tiotropium.1,2
Since these initial communications, FDA has completed its analysis of the Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial. UPLIFT was a large, 4-year clinical trial that compared Spiriva HandiHaler to placebo in 5,992 patients with COPD.
In the UPLIFT trial, there was no significant increase in the risk of stroke [0.95 (95% CI 0.70, 1.29)], heart attack [0.73 (95% CI 0.53, 1.00)], or cardiovascular death [0.73 (95% CI 0.56, 0.96)] between Spiriva HandiHaler and placebo.
In November 2009, the FDA Pulmonary - Allergy Drugs Advisory Committee also reviewed data from the UPLIFT trial and voted that the UPLIFT findings adequately resolve the potential safety concerns for stroke, heart attack and cardiovascular death.
1. Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease. JAMA 2008; 300 (12): 1439-1450.
2. Lee TA, Pickard S, Au DH et al. Risk of Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease. Annals of Internal Medicine 2008; 149: 380-390.