The French equivalent of the FDA, the Agence Francaise De Securite Sanitaire Des Produits De Sante, or AFSSAPS, said this past week that it will suspend the use of a diabetes drug, Actos (pioglitazone) as well as a combination drug including both Actos and metformin from sale in France "after considering the results of the study by CNAMTS [available in French on-line] at the request of AFSSAPS, confirming a small increased risk of bladder cancer patients treated with pioglitazone. This decision will take effect July 11, 2011 to allow patients to contact their doctor who will adjust their diabetic treatment."
The following day, the German regulators (Bundesinstitut für Arzneimittel und Medizinprodukte, or BfArM) also suspended the drug. And the European Medicines Agency (EMA) said that its Committee for Medicinal Products for Human Use, which had began a review of Actos-containing medicines in March, will now also assess the results of the French study. The EMA added a comment that "While this review is ongoing the CHMP is not recommending any changes to the use of pioglitazone-containing medicines."
Two recent publications in Diabetes Care also pointed to an association between the use of Actos (pioglitazone) and an increased risk of bladder cancer:
Urologic complications of diabetes, including bladder problems, are well-known, but a recent review article doesn't mention bladder cancer as a problem for people with diabetes. But it's been known for Actos, and the US label for Actos states:
In September 2010, the FDA announced their concern about the potential safety risk of bladder cancer with Actos, and pointed out that the manufacturer, Takeda, is conducting a 10-year study to assess the long-term risk of bladder cancer associated with Actos. At the five-year mark, the data showed no overall statistically significant association between Actos exposure and bladder cancer risk, but "an increased risk of bladder cancer was observed among patients with the longest exposure to Actos, as well as in those exposed to the highest cumulative dose of Actos."
As of today, I can find no information on the Internet that the FDA has yet issued a statement in response to the French and German actions; I suspect that if they do, their response will be like that of the EMA, described above.
What should patients taking Actos do? The FDA last year suggested the following advice for patients taking Actos:
Sounds like a reasonable set of recommendations to me.
Update June 19:
The FDA posted an Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer on June 15. They indicate that use of Actos may be associated with an increased risk of bladder cancer in patients who take the drug for more than a year. The Actos label will be updated to include this warning.