Actos Use Linked to Bladder Cancer

On June 15, 2011, the U.S. Food and Drug Administration (FDA) issued a drug safety communication warning patients and health professionals that use of pioglitazone (Actos—Takeda) for more than 1 year may be associated with an increased risk of bladder cancer. Patients who were on pioglitazone therapy for more than 12 months had a 40% increased risk of bladder cancer compared with patients who had never used the drug.

The active ingredient in Actos® is also contained in other drugs, namely Actoplus Met®, Actoplus Met XR®, and Duetact®

Oral diabetes medication Actos® (generic name pioglitazone) is made by Takeda Pharmaceutical Company and co-marketed in the United States by Eli Lilly Pharmaceuticals. Actos® and related drugs are used to control type-2 diabetes in patients whose condition is not adequately controlled by diet and exercise alone.

Actos® belongs to a class of drugs called Thiazolidinedione drugs, which help to treat Type-2 diabetes by lowering blood glucose levels and increasing the body’s sensitivity to insulin. This drug may be prescribed alone (as Actos®) or in combination with other active ingredients such as metformin (sold as Actoplus met) or glimepiride (sold as duetact). A patient’s drug regiment may also include insulin or other medications in addition to those containing pioglitazone.

Type-2 diabetes, which affects approximately 18 to 20 million Americans, is characterized by high blood glucose levels caused by the body’s inability to properly use insulin. This disease, left untreated, can lead to blindness, kidney problems, and cardiovascular disease.

According to the website EHealthMe conducted a study on August 17, 2011 regarding the side effects of taking Actos and the bladder cancer risk. According to the report, 22,512 reported side effects when taking Actos and 0.22% have bladder cancer. The largest concentration (approx. 43%) were using Actos between 2-5 years before having Bladder Cancer with the next largest concentration (approx. 29%) used Actos between 1-6 months.

In June 2011, the Type 2 Diabetes drug Actos (piogliatazone) had its sales suspended by medical regulators in France and Germany because of a possible bladder cancer risk. The French and German decisions to ban the drug came after a study commissioned by the French Medicines Agency found that people taking Actos were more likely to develop bladder cancer, an aggressive form of cancer. The study examined cancer rates in some 155,000 people taking Actos in France from 2006 to 2009 and 1.3 million other diabetics who were not receiving the drug. The study found about a 22 percent higher risk of bladder cancer in those taking the drug compared with diabetics taking other drugs. The bladder cancer risk was highest in those receiving a cumulative dosage of 28,000 mg or more during the study period.

Also in June 2011, the U.S. Food & Drug Administration (FDA) announced it was reviewing Actos for a possible bladder cancer risk in September 2010. At the time the agency said early data from a 10-year study submitted by Takeda, the maker of Actos, had not indicated a statistically significant association between exposure to the drug and bladder cancer risk. However, there was some evidence that patients taking Actos at least two years or at the highest cumulative doses (>28,000 mg) did face a greater danger from bladder cancer.

In May 2011, another study, this time looking at Adverse Event reports to the FDA between 2004-2009, suggested that Actos patients faced a "disproportionate risk” of bladder cancer. The study looked at a half million side effect reports associated with various diabetes medications and found that a fifth of those involving bladder cancer occurred in patients using the drug.

ACTOS is a prescription medication used with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes. ACTOS is not for patients with type 1 "juvenile" diabetes or diabetic ketoacidosis.

ACTOS works on two of the common problems that lead to high blood sugar in type 2 diabetes.

1. It helps your body better use the insulin it makes
2. It also stops your liver from making more sugar when it doesn’t need to

By treating these problems, the sugar in your blood can get to where it needs to go so it doesn’t continue to build up in the bloodstream. Certain patients with heart failure should not start taking ACTOS. Do not take ACTOS if you are allergic to any of its ingredients.

ACTOS can be added to certain diabetes medications such as metformin, sulfonylurea, or insulin for additional help to lower your blood sugar. When taking ACTOS with insulin or other diabetes medications, especially sulfonylureas, low blood sugar may occur. Talk to your doctor if low blood sugar is a problem for you. When taking ACTOS with insulin, the chance of fluid retention is increased, which may lead to or worsen heart failure. You should tell your doctor right away if you develop fluid retention, especially in the ankles or legs.

ACTOS also comes in a combination tablet with either metformin or a sulfonylurea. Learn more about ACTOplus met, ACTOplus met XR, and duetact.

ACTOS is a once-a-day pill that can help improve your blood sugar control.

Please see Important Safety Information, including warnings about heart failure and lactic acidosis, below.

Many people with type 2 diabetes have high levels of blood fats (triglycerides) and low levels of good cholesterol (HDL-C). Along with lowering your blood sugar, ACTOS may improve the amount of good cholesterol and blood fats in your body. It has little effect on bad cholesterol (LDL-C) or total cholesterol levels. ACTOS is not a substitute for cholesterol medication. The benefits of these cholesterol changes have not been proven. Talk to your doctor to gain a better understanding of your cholesterol numbers.

American Diabetes Association:

Cholesterol goals for people with diabetes

• Blood fats, or triglycerides - Less than 150 mg/dL
• Good cholesterol, or HDL-C - Greater than 40 mg/dL in men; Greater than 50 mg/dL in women
• Bad cholesterol, or LDL-C - Less than 100 mg/dL

Attorneys for Takeda Pharmaceuticals indicate that the drug maker supports a request to have all federal Actos bladder cancer lawsuits consolidated for pretrial litigation, but disagrees about where the claims should be centralized.

On September 29, Actos lawyers for Takeda filed a response with the U.S. Judicial Panel on Multidistrict Litigation, indicating that they agree with plaintiffs that an MDL, or multidistrict litigation, should be formed, but requested that the cases be transferred to the Northern District of Illinois or Western District of Louisiana.

A motion to consolidate the Actos bladder cancer litigation was first filed on August 31, by plaintiff Glen Weant and his wife, Nina. Weant requested that all federal Actos lawsuits be transferred to the U.S. District Court for the Southern District of Illinois before Judge G. Patrick Murphy. Since then, additional plaintiffs have filed responses proposing other U.S. District Judges to preside over the litigation.

The first lawsuit over Actos was filed on July 29, 2011. According to documents filed by Takeda last week, the drug maker is now aware of at least 54 cases that have been filed in federal district courts throughout the United States. In addition, as Actos attorneys for plaintiffs continue to review and file new complaints on behalf of people diagnosed with bladder cancer after taking the type 2 diabetes drug, the number of claims is expected to continue to grow.

All of the complaints involve similar allegations that side effects of Actos caused users to develop bladder cancer. Plaintiffs argue that Takeda failed to properly research the medication or warn about the risk.

Although Takeda’s attorneys indicated that they do not agree with many of the assertions contained in the Plaintiffs’ filings, they agreed that the cases fit the requirements for an MDL and that consolidation would help prevent contradictory rulings and duplicative discovery. It would also serve the convenience of counsel, witnesses, plaintiffs and defendants, according to the drug maker’s response.

Takeda has proposed that the Actos litigation be consolidated in the Northern District of Illinois, where the drug maker is headquartered and where much of the company’s records are located. As an alternative, the drug maker proposed the Western District of Louisiana as an appropriate location for the Actos MDL to be centralized, as there are at least 16 cases already pending in that district.

Actos (pioglitazone) was approved by FDA to treat Type 2 Diabetes in July, 1999. It is a once-a-day pill that increases the body’s sensitivity to insulin. The medication has grown in popularity in recent years, after studies linked it’s primary competitor, Avandia, to an increased risk of heart attacks and death. Last year, Actos generated $4.3 billion in sales for Takeda Pharmaceuticals.

FDA officials began reviewing the potential risk of Actos bladder cancer problems in September 2010, after interim data from an on-going 10 year study found that users may face an increased risk the longer they take the drug. Data from the study conducted by Takeda Pharmaceuticals, the makers of Actos, indicated that after 24 months, the rate of exposure and the increased risk of bladder cancer reached statistical significance.

In June, an Actos recall was issued in France after a review of public insurance data identified an increased incidence of bladder cancer with Actos use.

The European Union’s European Medicines Agency (EMA) also conducted a review and confirmed the bladder cancer risk, calling for new warnings and a six-month review of every patient on Actos. The EMA suggested that Actos bladder cancer risk could be reduced by appropriate patient selection and exclusion.

Since then, the number of lawsuits over Actos has been steadily increasing in federal district courts throughout the United States. The U.S. Judicial Panel on Multidistrict Litigation is expected to schedule oral arguments on the motion to consolidate the cases at the next hearing, which will be held on December 1 in Savannah, Georgia.