European Drug Regulator EMA Recommended New Actos Contra-Indications And Warnings In July 2011
(Posted by Tom Lamb at DrugInjuryWatch.com)
UPDATE: "European Medicines Agency clarifies opinion on pioglitazone and the risk of bladder cancer" (10/21/11, EMA Press Release)
On August 4, 2011 we learned that Takeda Pharmaceuticals America, Inc. had revised the prescribing information -- also called the package insert or label -- for its diabetes drug Actos (pioglitazone) and other anti-diabetic pioglitazone-containing medicines by means of this item, "FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines":
The U.S. Food and Drug Administration (FDA) is informing the public that the Agency has approved updated drug labels for the pioglitazone-containing medicines to include safety information that the use of pioglitazone for more than one year may be associated with an increased risk of bladder cancer. FDA previously communicated these labeling changes to the public on June 15, 2011. [See: "Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder"]....
A couple of weeks earlier, on July 21, 2011, the European Medicines Agency (EMA) had recommended that Takeda put new warnings on the Actos label about possible links to bladder cancer in Europe.
As for the action taken by the drug company Takeda and the FDA here in the U.S., the Actos label revised in July 2011 after FDA approval adds this new part to Section 5, "WARNINGS AND PRECAUTIONS":
5.5 Urinary Bladder Tumors
Tumors were observed in the urinary bladder of male rats in the two-year carcinogenicity study [see Nonclinical Toxicology (13.1)]. In two 3-year trials in which ACTOS was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of bladder cancer in patients taking ACTOS compared to 5/3679 (0.14%) in patients not taking ACTOS. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on ACTOS and two (0.05%) cases on placebo.
A five-year interim report of an ongoing 10-year observational cohort study found a nonsignificant increase in the risk for bladder cancer in subjects ever exposed to ACTOS, compared to subjects never exposed to ACTOS (HR 1.2 [95% CI 0.9 – 1.5]). Compared to never exposure, a duration of ACTOS therapy longer than 12 months was associated with an increase in risk (HR 1.4 [95% CI 0.9 – 2.1]), which reached statistical significance after more than 24 months of ACTOS use (HR 1.4 [95% CI 1.03 – 2.0]). Interim results from this study suggested that taking ACTOS longer than 12 months increased the relative risk of developing bladder cancer in any given year by 40% which equates to an absolute increase of 3 cases in 10,000 (from approximately 7 in 10,000 [without ACTOS] to approximately 10 in 10,000 [with ACTOS]).
There are insufficient data to determine whether pioglitazone is a tumor promoter for urinary bladder tumors. Consequently, ACTOS should not be used in patients with active bladder cancer and the benefits of glycemic control versus unknown risks for cancer recurrence with ACTOS should be considered in patients with a prior history of bladder cancer.
For background about the association between Actos and bladder cancer we refer you to our earlier article, "Actos-Related Bladder Cancer: June 2011 Review Of Regulatory Actions And Safety Warnings", concerning this emerging drug safety issue.
We remind patients using Actos that the FDA advises you should not stop taking any prescription medication, including Actos, before talking to your doctor.
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