Warning on pioglitazone and bladder cancer

A warning is being added to the label of diabetes medication pioglitazone (Actos) about the drug's possible association with bladder cancer, the FDA announced last week.

The warning is based on an interim analysis of an ongoing 10-year study by the manufacturer. The study found overall that patients who had taken pioglitazone had no increase in bladder cancer compared to those who had never been exposed. However, compared to never taking pioglitazone, a duration of pioglitazone therapy longer than 12 months was associated with a 40% increase in risk (HR, 1.4; 95% CI, 0.9 to 2.1), the FDA reported.

Use of the drug was recently suspended in France due to the results of a different study, which found statistically significant increases in bladder cancer with pioglitazone compared to other diabetes drugs (HR, 1.22; 95% CI, 1.03 to 1.43). The results also showed a dose effect for a cumulative dose greater than 28,000 mg (HR, 1.75; 95% CI, 1.22 to 2.5) and for exposures longer than 1 year (HR, 1.34; 95% CI, 1.02 to 1.75).

In the new warning, the FDA recommends that clinicians not use pioglitazone in patients with active bladder cancer and use it cautiously, weighing risks and benefits, in patients with a prior history of bladder cancer. Patients should be encouraged to report any signs or symptoms of blood in the urine, urinary urgency, pain on urination, or back or abdominal pain. Pioglitazone is also sold in combination with metformin (Actoplus Met, Actoplus Met XR) and glimepiride (Duetact).