Actos (pioglitazone) is an antidiabetic medication used to treat Type 2 diabetes. It is manufactured by Takeda Pharmaceuticals, a Japanese company and co-marketed by U.S. pharma giant, Eli Lilly. Actos was approved in 1999 and has been the subject of numerous FDA warnings, restrictions and recalls in other countries. Concerns have been raised over a possible two-fold increase in bladder cancer, a high risk for congestive heart failure, a doubling in bone fracture risk, increased risk for lactic acidosis and kidney disease and other serious side effects which may be life threatening.
Actos has been a top-selling antidiabetic for much of it’s history and was in the list of “Top 10 Drugs in the U.S.” during its peak sales years. From 2007 to 2011, Actos sales averaged $3 to 4 billion per year and accounted for 25% of Takeda’s revenue.
Over 10,000 lawsuits have been filed by plaintiffs injured by Actos and in 2015, the company agreed to settle over many of those claims for a total of $2.4 billion. By the time of the 2015 settlement, sales of the drug had exceeded $25 billion with over 100 million prescriptions filled in the U.S.
Actos Bladder Cancer Risk
Prior to its approval, animal studies showed pioglitazone, the active ingredient in Actos, caused increased bladder tumor grown in male rats. After approval, results of a three-year safety study showed an increase in bladder cancer risk in humans. Because of these results, the FDA ordered Takeda to conduct an additional 10-year bladder cancer study.
After interim results became available at the 5-year point, the FDA required that Takeda increase warnings about bladder cancer. Final results from the 10-year safety study confirm previous reports that Actos poses an increased risk for bladder cancer.
Serious Adverse Events
In addition to bladder cancer, Actos may pose additional risks which can be harmful, permanent or life-threatening.
- Bone Fracture Risk – Actos may increase the risk of bone fracture by two or more times. The risk appears to be greater in women but may include men and occurs mostly in the lower legs, arms or hips and is likely related to Actos’ effect on bone tissue growth.
- Congestive Heart Failure – Actos may double the chance of heart failure. In 2007, the FDA required the addition of a “black-box warning” to be included on information for Actos regarding the risk of Congestive Heart Failure.
- Chronic Kidney Disease – Taking Actos may increase the risk of kidney disease by as much as 400 percent. Kidney disease cause high blood pressure, worsen cardiac problems and may result in a need for kidney replacement or end stage renal disease (ESRD) which may cause death.
- Macular Edema – Macular edema may result in damage to the retina and permanent blindness. The risk of macular edema is increased in diabetic patients but a 2009 study showed that the medication doubles the risk of developing macular edema and blindness.
In addition to injury claims by patients, in 2012, Takeda was accused of wrongdoing by one of its safety consultants. The pharmacovigilance employee claimed that the company knew about Actos link to several types of cancer but failed to act.
Court documents state that Takeda conducted a survey of doctors asking if a bladder cancer warning would affect their likelihood of prescribing a diabetes drug. The results suggested that Actos sales would plummet. It is speculated that Takeda knowingly postponed adequate warnings to continue making high profit.
In a 2014 trial, evidence arose that Takeda destroyed documents related to the case. Shortly before the trial began, a judge, believing the company acted in bad faith, ruled the jury must hear claims that files and documents were destroyed after employees were warned to save all pertinent information. The company admitted they were unable to find files compiled by 46 current and former employees involved with the development, marketing, and sale of the drug, including information from two of the company’s directors.
The 2014 federal Actos lawsuit, filed in Louisiana, resulted in one of the biggest damages verdicts to date when a Louisiana jury ruled Takeda Pharmaceuticals must pay $9 billion in punitive damages. The verdict requires Eli Lilly to pay $3 billion of the total damages. The damages were later reduced to a total of $38.5 million, still one of the largest settlements in drug liability to date.
Facing thousands of lawsuits in federal, state and local courts, and having already paid millions of dollars to a handful of plaintiffs in trial cases, Takeda opted to settle nearly 9,000 cases by setting aside $2.4 billion. About 5,000 federal multi-district litigation (MDL) cases and an estimated 4,000 state and local Actos lawsuit cases were eligible for an Actos settlement.
Actos FDA Warning
In June 2011, the FDA issued a Drug Safety Communication warning user of the increased risk of Actos bladder cancer in patients who use the drug for longer than one year. Additionally, warnings of bladder cancer were added to the Actos label under the “Warnings and Precautions” section. In addition to warnings regarding bladder cancer, the FDA also required a black-box warning for both Actos and Avandia stating the risks of congestive heart failure. This Avandia and Actos black-box warning was also issued in June 2011.
Actos is similar to another Type 2 diabetes drug, Avandia, made by GlaxoSmithKline. In addition to some of the risks shown with Actos, Avandia was associated with an increased risk of heart attacks and vascular disorders. Due to life-threatening events, both Avandia and Actos were recalled in parts of the EU. In the U.S. however, neither Avandia nor Actos have been recalled and other than warnings on prescribing labels, all restrictions have been lifted.
Actos Lawsuit Claims
Actos lawsuits have claimed that Takeda Pharmaceuticals and Eli Lilly failed to adequately warn consumers of the dangers of using Actos. Plaintiffs also claimed that Takeda and other involved parties did not conduct adequate research on the drug’s safety, resulting in Actos patients suffering life-threatening side effects from taking the drug.
Patients or family members of those who were injured by a drug such as Actos, may be eligible for compensation for the expenses, pain, and suffering associated with their injuries. There are no guarantees as each case is unique and must be evaluated separately by a legal expert.