The Food and Drug Administration said August 5 that it had approved new labels for the diabetes drug pioglitazone to include warnings about bladder cancer risk.
The announcement follows the agency’s June 15 statement explaining its intention to craft new warnings on pioglitazone in light of interim findings from a 10-year epidemiologic study (Diabetes Care 2011;34:916-22) that saw an increased risk of bladder cancer among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of the drug.
The study showed no significant increase in the risk for bladder cancer in patients ever exposed to pioglitazone, compared with those never exposed to pioglitazone (hazard ratio, 1.2). By contrast, a year or more of pioglitazone therapy was associated with a 40% increase in risk (HR, 1.4).
The new warnings recommend that pioglitazone, marketed in the United States as Actos (or in combination with metformin as Actoplus Met, and with glimepiride as Duetact) not be given to patients with active bladder cancer and that the drug be used with caution in those with prior bladder cancer.
The updated labels recommend that patients contact a health care professional if they experience "any sign of blood in the urine or a red color in the urine or other symptoms such as new or worsening urinary urgency or pain on urination since starting pioglitazone, as these may be due to bladder cancer."
An ongoing study in France resulted in the suspension of pioglitazone there in June and prompted a broader review by the European Medicines Agency.
On July 21, the European Medicines Agency announced its intention to alter warnings on pioglitazone to reflect the known bladder cancer risk; however, the agency stopped short of recommending that its marketing be suspended in the European Union, concluding in that the risk-benefit profile of pioglitazone continued to be favorable if risks were "reduced by appropriate patient selection and exclusion."