Tiotropium (marketed as Spiriva HandiHaler)
Audience: Pulmonary care health professionals and patients
[01/14/2010] FDA issued a Follow-Up to the previous Early Communications issued in 2008, 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.
[UPDATE 10/07/2008] FDA informed healthcare professionals that FDA has reviewed preliminary data from UPLIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium), a large, 4-year, placebo controlled clinical trial with Spiriva HandiHaler in approximately 6000 patients with chronic obstructive pulmonary disease. The preliminary results reported by Boehringer Ingelheim to the FDA showed that there was no increased risk of stroke with tiotropium bromide compared to placebo.
Two recent publications reported increased risk for mortality and/or cardiovascular events in patients who received tiotropium or inhaled anticholinergics. Both studies examined cardiovascular outcomes.
FDA expects to receive the complete report for UPLIFT in November 2008. Results from this trial will also help to address some issues raised about tiotropium in the two recent publications. Due to the amount of data collected in UPLIFT, a complete review of the results could take several months, at which time FDA will update this communication with the final results of the UPLIFT analysis, as well as all the available data regarding tiotropium and stroke risk.
[Posted 03/18/2008] Boehringer Ingelheim and FDA notified healthcare professionals that ongoing safety monitoring has identified a possible increased risk of stroke in patients who take Spiriva. This product contains tiotropium bromide and is used to treat bronchospasm associated with chronic obstructive pulmonary disease. Boehringer Ingelheim reported to the FDA that it has conducted an analysis of the safety data from 29 placebo controlled clinical studies (“pooled analysis”). Based on data from these studies, the preliminary estimates of the risk of stroke are 8 patients per 1000 patients treated for one year with Spiriva, and 6 patients per 1000 patients treated for one year with placebo. This means that the estimated excess risk of any type of stroke due to Spiriva is 2 patients for each 1000 patients using Spiriva over a one year period.
It is important to interpret these preliminary results with caution. FDA is working with Boehringer Ingelheim to further evaluate the potential association between Spiriva and stroke. FDA has not confirmed these analyses and while pooled analyses can provide early information about potential safety issues, these analyses have inherent limitations and uncertainty that require further investigation using other data sources. Patients should not stop taking Spiriva HandiHaler before talking to their doctor, if they have questions about this new information. This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.
[UPDATE 01/14/2010 - Follow-Up to the October 2008 Updated Early Communication - FDA]
[UPDATE October 07, 2008 - Early Communication about an Ongoing Safety Review - FDA]