Diabetes affects more than 29 million Americans and more cases of the disease are diagnosed each year. Between 1980 and 2014, the number of adults in the US with newly diagnosed diabetes more than tripled. With so many people affected by the disease, it’s no wonder pharmaceutical companies were enjoying record profits from drugs developed to treat diabetes. One of those drugs was Actos. Once a blockbuster drug, bringing in billions of dollars for its manufacturer, sales of Actos dropped significantly after studies came out showing the risk for serious side effects, including certain cancers and heart failure.

What is Actos?

Actos is a prescription medication used to treat patients with type II diabetes. More than 29 million Americans had either Type I or Type II diabetes in 2012, and an estimated 1.4 million Americans are diagnosed with diabetes every year, according to the American Diabetes Association. Type II diabetes is the most common form of the disease, and is controlled using a combination of diet, exercise and prescription medications like Actos.

What is Actos used to treat?

Actos is indicated for the treatment of type II diabetes along with diet and exercise. Actos helps regulate blood sugar (glucose) levels in people with type II diabetes.  People with type II diabetes have blood sugar levels that are higher than normal, a condition called hyperglycemia, because their bodies do not use insulin properly. The pancreas makes insulin to keep blood sugar at normal levels. Insulin resistance causes the pancreas to make extra insulin at first, in an effort to keep up with rising blood sugar levels. Over time, however, the pancreas is unable to keep up and can’t make enough insulin to maintain normal blood sugar.

How does Actos work?

Actos depends on the presence of insulin for its mechanism of action. The main ingredient in Actos, pioglitazone, belongs to the class of drugs called thiazolidinediones. These drugs work by activating certain receptors in the body which cause an increase in the storage of fatty acids in fat cells. The storage of fatty acids in fat cells reduces the amount of fatty acids present in the blood, which causes cells to use carbohydrates like glucose as their energy source.

Who makes Actos?

Actos is manufactured by Japan-based Takeda Pharmaceutical Company. Takeda is the largest pharmaceutical company in Japan and is one of the 15 top pharmaceutical companies in the world. In 2015, Takeda brought in roughly $17 billion in revenue.

When was Actos approved by the FDA?

The Food and Drug Administration approved Actos on July 15, 1999. It was one of two thiazolidinediones approved that year, the second being Avandia (rosiglitazone), which was put under selling restrictions in the US due to its potential increased risk for cardiovascular events.

What are the possible side effects of Actos?

Like all prescription medicines, Actos has potential side effects. According to the drug’s package insert, the most common side effects of Actos include:

  • Cold-like symptoms (upper respiratory tract infections)
  • Headache
  • Sinus infection
  • Muscle pain
  • Sore throat

Other more serious adverse effects can also occur while taking Actos. These include:

  • Fluid retention that can lead to edema (swelling) and weight gain
  • Hypoglycemia (low blood sugar)
  • Liver problems
  • Bone fractures
  • Diabetic eye disease with swelling in the back of the eye
  • Bladder cancer
  • Heart failure

Are Actos users at greater risk for heart failure?

Heart failure is a potential risk for all drugs belonging to the thiazolidinedione classification, including Actos.

According to the drug’s label, the risk for congestive heart failure may be increased due to Actos’ potential to cause fluid retention. Merely two years after Actos was approved, Takeda was required to update the drug’s label to include the potential increased risk of cardiac failure.

The label change came shortly after Health Canada issued an advisory about the risk of heart failure in patients taking Actos. A letter published in 2002 in the Canadian Medical Association Journal by one of its editorial fellows said “patients should be warned that thiazolidinedione medications [such as Actos] may lead to the development or exacerbation of congestive heart failure.”

Studies published subsequently in various medical journals also showed an increased risk for cardiac failure in patients taking Actos and other thiazolidinediones.

Congestive heart failure is a serious condition in which the heart cannot pump enough blood to meet the body’s needs. It can be fatal in some cases.

Symptoms of congestive heart failure may include:

  • Dizziness, fatigue and weakness
  • Fluid retention/swelling
  • Rapid or irregular heartbeats
  • Shortness of breath

Are Actos users at greater risk for bladder cancer?

Roughly 10 years after Actos was approved by the FDA, the agency began reviewing data from a then-ongoing 10-year study being conducted by the manufacturer of Actos.

Based on the study’s findings, the FDA said there may be an increased risk of developing bladder cancer when taking Actos for more than one year and there may be a 40 percent increased risk of developing bladder cancer when taking the drug for two years or more.

Numerous other studies have been published indicating an increased risk for bladder cancer in diabetes patients taking Actos, a risk not associated with other thiazolidinediones.

Depending on the stage of the cancer at diagnosis, bladder cancer can be deadly.

According to the American Cancer Society, signs and symptoms of bladder cancer in its early stages may include:

  • Blood in urine
  • Having to urinate more often
  • Pain or burning during urination
  • Feeling the need to go right away
  • Trouble urinating or weak urine stream

Signs and symptoms of advanced bladder cancer may include:

  • Being unable to urinate
  • Lower back pain on one side
  • Loss of appetite and weight loss
  • Feeling tired or weak
  • Swelling in the feet
  • Bone pain

Has the FDA issued any warnings about Actos?

The FDA informs doctors and consumers about potential safety issues regarding drugs and medical devices through safety communications. The FDA has issued several safety communications regarding Actos since the drug’s approval more than 15 years ago.

‘Black Box’ Warning: Congestive Heart Failure

The FDA first warned about the increased risk for heart failure while taking Actos in 2002, just two years after the drug was approved. The agency required the risk be included on the drug’s label, but it would be another five years before the risk was given more prominence on the label.

In 2007, the FDA required a black box warning – the strongest safety warning issued by the FDA short of a recall – be put on the Actos label indicating the risk of congestive heart failure while taking the drug.

The boxed warning indicates the drug could cause or exacerbate congestive heart failure in some patients; patients should be monitored closely for signs and symptoms of heart failure after starting or increasing the dose of Actos; Actos is not recommended in patients with symptomatic heart failure; and patients with New York Heart Association class III or class IV heart failure should not take Actos.

Risk of Bladder Cancer

In a series of safety communications, the FDA warned consumers about the potential increased risk for bladder cancer while taking Actos.

The first communication, issued in September 2010, indicated the agency was looking into the possible increased risk after a then-ongoing 10-year study found an association between Actos and bladder cancer.

In June 2011, the agency issued a second, updated communication indicating the association between Actos use and the increased risk for bladder cancer was strong enough to include the risk on the drug’s label. Two months later, the agency issued a third update indicating it had approved new labels for Actos which included the warning about bladder cancer.

Has Actos been recalled?

Generic versions of Actos, sold under the generic name pioglitazone, have been the subject of at least three class II recalls between 2013 and 2015. Two of the recalls were initiated due to labeling mistakes, while the third was initiated due to cross-contamination with penicillin. Class II recalls are reserved for products which may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.

European countries pull Actos

Actos has never been recalled or pulled from the market in the US due to concerns over the drug’s potential risks. However, at least two European countries have suspended sales of Actos after learning of the drug’s potential to cause bladder cancer. On June 9, 2011, after conducting a study of its own, the French government pulled Actos from the French market, and Germany followed suit the very next day.

Are there generic versions of Actos available?

Takeda Pharmaceuticals lost its exclusivity over Actos in August 2012, clearing the way for generic equivalents to saturate the market. There are at least 12 other pharmaceutical companies now selling generic versions of Actos in the US. Generics are nearly identical to their brand-name counterparts and are generally cheaper.

How do you take Actos?

Actos is a once-daily tablet available in three different doses. Actos is taken orally (by mouth) and can be taken without regard to meals. The recommended starting dosage is 30 mg once per day. Those with congestive heart failure should start at 15 mg once daily, according to the drug’s label.

Actos is available in 15 mg, 30 mg and 45 mg doses.

It is possible to overdose on Actos. Seek emergency medical help if you overdose on Actos. Signs and symptoms of an Actos overdose include:

  • Extreme weakness
  • Blurred vision
  • Sweating
  • Trouble speaking
  • Tremors
  • Stomach pain
  • Confusion
  • Convulsions

Are there lawsuits against the makers of Actos?

Following the news of an increased risk of bladder cancer while using Actos, patients began filing lawsuits against the maker of the drug, Takeda Pharmaceuticals.

So far, nine lawsuits have been tried in the US, five of which resulted in verdicts in favor of Takeda and four of which resulted in verdicts in favor of the plaintiffs. Most of these lawsuits were tried in state courts, with one being tried in federal court as part of a multi-district litigation (MDL).

Multi-district Litigation

The first case in the MDL, which was tried in 2014, resulted in a verdict in favor of the plaintiffs. Jurors awarded the plaintiff in this bellwether trial $1.475 million in compensatory damages and a whopping $9 billion in punitive damages.

The compensatory damages were to be split 75-25 between Takeda and Eli Lilly, another pharmaceutical company with a stake in the Actos drug; the punitive damages were to be split as well, with Takeda responsible for $6 billion and Eli Lilly responsible for $3 billion.

Following an appeal by Takeda, the verdict was later reduced from $1.475 million in compensatory damages to $1.25 million and from $9 billion to about $37 million in punitive damages. (Takeda would be responsible for $27.65 million of the total punitive damages, while Eli Lilly would be responsible for $9.22 million.)

State courts

In state courts, three juries have handed down verdicts in favor of the plaintiffs. In October 2014 and February 2015, two trials held in a Philadelphia County court resulted in a $2.05 million and a $3.7 million verdict, respectively. In November 2014, a jury in a Berkeley County, West Virginia courtroom found Takeda liable for one of the plaintiff’s claims and ordered the company to pay $155,000 in compensatory damages. Takeda has appealed all of the aforementioned verdicts.

Lawsuits abroad

There are class action lawsuits pending in Canada against Takeda and Eli Lilly regarding the increased risk for bladder cancer while taking Actos. A claim has also been filed in Germany seeking compensation for bladder cancer. A similar claim filed in France has already been resolved.

 Takeda agrees to settle

On April 28, 2015, Takeda announced it would agree to settle all remaining Actos bladder cancer litigation pending in US courts if 95 percent of litigants agreed to take the settlement.

The settlement agreement includes all cases pending as of the date of the settlement, as well as any unfiled claims of claimants who are represented by an attorney at the date of the settlement and three days after.

Takeda set aside $2.37 billion for the settlement. If 97 percent of litigants agree to it, that number would go up to $2.4 billion.

I suffered serious injury after taking Actos. Can I file a lawsuit?

Lawsuits are still being filed by patients who were harmed by Takeda’s type II diabetes drug Actos. With the drug company’s announcement to settle in 2015, however, the time to file a lawsuit may soon be coming to a close.

If you or someone you love was injured while taking Actos, you may be entitled to compensation but you need to act now. Call National Injury Help today at 1-800-214-1010 for a free case evaluation or use the form on the right-hand side of your screen.