FDA Actos Warnings: Bladder Cancer, Heart Failure

Actos (pioglitazone) is promoted as an effective treatment for regulating blood sugar levels of patients with type 2 diabetes, but the prescription drug has been associated with serious side effects since it entered the market. After patients started using Actos in 1999, the FDA began to receive adverse event reports that associated the drug with an increased risk of cardiovascular problems, including congestive heart failure. As time progressed, clinical studies also linked Actos to additional medical complications such as bladder cancer, bone fractures, and liver failure.

By 2007, an FDA Actos warning was issued to advise healthcare providers that the prescription drug may cause heart failure and other adverse health consequences for patients. Takeda Pharmaceuticals was required to update the Actos warning labels to display a “black box” to alert patients of the serious risks associated with taking the medication.

Medical studies establish link between Actos and heart failure

In August 2007, the FDA decided to issue the Actos heart failure warning based on the results of post-marketing studies that concluded the prescription medication increased the risk of congestive heart failure and heart attacks.

In 2007, a study published in The Journal of the American Medical Association examined the relationship between Actos and heart failure. The researchers analyzed 16,390 patients who used the drug from a period of 4 months to 3.5 years. According to the study’s results, the risk of developing serious heart failure was increased by 2.3% amongst the patients who used Actos.

A separate 24-week study comprised of 5,238 patients evaluated the risk factors associated with Actos and heart failure. The researchers proceeded to follow-up with the patients for an average period of 34.5 months to continue monitoring their health. According to the study’s results, 9.9% of the patients who took Actos received overnight treatment in the hospital for congestive heart failure; 5.7% of the patients experienced serious heart failure; and 1.5% of the patients died after suffering from heart failure.

Actos warning: heart failure

When the FDA issued the alert regarding the safety risks, it wanted to ensure that patients and their physicians were aware of potential Actos side effects, and were able to make an informed decision regarding medical treatment.

Recommendations and information provided in the Actos FDA warning:

• Actos may cause or exacerbate the risk of patients suffering from heart failure
• Medical professionals should carefully monitor patients for signs of heart failure after they start taking Actos
• Medical professionals should administer proper treatment to patients with heart failure and consider reducing the Actos dosage or discontinue use of the drug
• Actos is not recommended for patients with pre-existing heart conditions or symptoms associated with heart failure
• Patients need to be aware that Actos can cause fluid retention or edema – conditions that may contribute to heart failure
• Patients should report any signs or symptoms of heart failure and other adverse health conditions to their physician

Actos and bladder cancer

Heart failure was one of the major side effects associated with Actos, but as patients started using the drug for longer periods of time, reports of patients suffering from bladder cancer began to accumulate. In 2005, a three-year study called PROactive concluded that patients had a greater risk of developing bladder cancer when they used Actos compared to other diabetes drugs. Takeda Pharmaceuticals allegedly knew about the association between Actos and bladder cancer, but chose not to disclose this information when the study’s results were published.

On June 9, 2011, the European Medicines Agency stated that France would limit access to Actos after a medical study showed that taking the drug for more than a year increased the risk of males developing bladder cancer. The researchers who conducted the French medical study evaluated 1.5 million diabetic patients for a period of four years. Germany also decided to suspend the distribution of Actos after reviewing the results from the French medical study.

On June 15, 2011, the FDA announced that taking Actos for longer than a year may be associated with a greater risk of bladder cancer. The FDA decided to issue the safety announcement based on the results from an ongoing 10-year Kaiser Permanente study that evaluated the link between Actos and bladder cancer. Based on the five-year interim results, there was an increased risk of bladder cancer for patients who received the highest doses of Actos and used the drug for the longest period of time.

The FDA also stated that it planned on performing an in-depth review of the results from the French study.

Updated Actos warning for bladder cancer risk

The FDA approved updates to the Actos warning labels regarding the increased risk of bladder cancer.

The FDA Actos warning labels state:

• Using Actos for more than a year may be associated with a higher risk of bladder cancer
• Patients with an active case of bladder cancer shouldn’t use Actos
• Medical professionals should be cautious when prescribing Actos to patients with a previous history of bladder cancer
• Patients should contact their physician if they notice signs or symptoms of bladder cancer such as blood in the urine, pain while urinating, or urgent need to frequently urinate

How the Actos warning impacts lawsuits

Even though Actos was approved by the FDA in 1999 and was the subject of numerous adverse event reports and medical studies linking the drug to severe side effects, it took several years before the FDA Actos warning was issued to patients and healthcare professionals. As a result, many people were unknowingly exposed to serious medical risks. Thousands of patients who were injured by the drug have filed Actos lawsuits against Takeda Pharmaceuticals in state and federal court.

The causes of action brought by a plaintiff’s Actos lawyer may include the manufacturer’s failure to warn about the safety risks, negligence, fraudulent concealment, and strict liability.

On December 29, 2011, the Actos lawsuits filed in federal court were consolidated into multidistrict litigation. More than 3,000 lawsuits are being handled in the U.S. District Court for the Western District of Louisiana. The first trial for the Actos multidistrict litigation is scheduled to start in January 2014.