FDA Again Warns of Bladder Cancer Risk With Pioglitazone-Containing Medications

Agency updates labels with additional safety data

As a result of an updated review, the FDA has concluded that the use of the type-2 diabetes (T2D) medication pioglitazone (Actos, Actoplus Met, Actoplus Met XR, Duetact, and Oseni) may be linked to an increased risk of bladder cancer. The labels of pioglitazone-containing medications already contain warnings about this risk, but the FDA has approved new label updates to describe additional studies that the agency has reviewed.

The FDA alerted the public about the possible risk of bladder cancer in September 2010 and in June 2011 based on interim results from a 10-year epidemiologic study. The agency changed the labels of pioglitazone-containing drugs in August 2011to include warnings about this risk, and required the manufacturer to modify and continue the 10-year study.

Pioglitazone is indicated to improve blood sugar control, along with diet and exercise, in adults with T2D. The drug works by increasing the body’s sensitivity to insulin. Untreated, T2D can lead to serious health problems, including blindness, nerve and kidney damage, and heart disease.

Health care professionals should not use pioglitazone in patients with active bladder cancer, and should carefully consider the benefits and risks before using pioglitazone in patients with a history of bladder cancer, according to the FDA.

Patients should contact their health care professionals if they experience any of the following signs or symptoms after starting pioglitazone, as these may be due to bladder cancer:

  • Blood or a red color in the urine
  • New or worsening urge to urinate
  • Pain when urinating

The FDA reviewed additional published studies evaluating the risk of bladder cancer in patients treated with pioglitazone. The results varied among the reviewed studies. For example, the 10-year epidemiologic study did not find an increased risk of bladder cancer with pioglitazone use, whereas another study did. In addition, a randomized controlled trial found an increased risk during the trial period; however, the risk did not persist when patients were followed after the trial was completed. Moreover, findings of these and other reviewed studies conflicted about whether the duration of use and/or total dose over time of pioglitazone influenced the risk of bladder cancer. The FDA also communicated in 2010 that bladder tumors were seen with pioglitazone exposure in animal studies. Overall, the data suggest that pioglitazone use may be linked to an increased risk of bladder cancer, the agency says.

The FDA urges health care professionals to report adverse events involving pioglitazone or other medications to the agency’s MedWatch program.

Source: FDA; December 12, 2016.