What is Actos?

Actos is the brand name of pioglitazone, a prescription drug used since 1999 to treat type 2 diabetes. It belongs to the class of drugs called thiazolidinediones (TZD), which treat diabetes by:

  • reducing insulin resistance
  • increasing cells’ sensitivity to insulin
  • reducing the amount of glucose made in the liver
  • aiding in the disposal of excess blood sugar.

The drug has also been used experimentally to treat non-alcoholic steatohepatitis (fatty liver).1 Actos is administered orally in a pill form, either 15 or 30 mg, taken once a day. Patients who don’t respond to this amount may be prescribed 45 mg a day.2

Other forms of Actos include:

  • Actoplus Met: combined with Metformin, another type-2 diabetes medicine.
  • Duetact: combined with Glimepiride, another type-2 diabetes medicine.

Takeda Pharmaceuticals, the largest pharmaceutical company in Asia and in the top 15 worldwide, began manufacturing Actos in 1999.3 When a similar TZD drug, rosiglitazone (Avandia), was restricted for use in the US and pulled from markets in Europe due to concerns over increased risks of congestive heart failure, Actos became the most widely-prescribed diabetes drug in the world.4

Pharmaceutical giant Eli Lilly began marketing the drug, and by 2008 Actos was the tenth best-selling drug in the US. Sales peaked in the year ending March 2011, with US sales alone bringing in $4.5 billion. The drug became an economic mainstay of manufacturer Takeda Pharmaceuticals, making up 27% of its revenue. According to court filings, the company has made more than $16 billion from Actos.5

Lawsuits and Verdicts

Those who are bringing lawsuits against Takeda claim that the company knew about cancer risks as early as 2004, and hid that information for seven years.9 Court documents reveal that Takeda destroyed massive amounts of documents belonging to top executives — a move that plaintiffs argue is a cover-up.10

Taking this evidence into consideration, judges and juries have tended to side generously with patients in the lawsuits. The first federal trial on this issue, which took place in Louisiana, concluded in April 2014 with a jury ordering Takeda to pay an astonishing $9 billion in punitive damages and $1.5 million in compensatory damages to a Terrence Allen, who had taken Actos and was later diagnosed with bladder cancer.11

Takeda’s lawyers eventually managed to get these amounts reduced by a judge to $36.8 million, but the message had been sent: the company could face massive liability for their behavior. For this reason, on April 1, 2015, Takeda made an offer to settle all claims that the company tried to hide the drug’s cancer risks. The settlement amounts to $2.2 billion dollars, and if accepted it will be one of the largest settlements of a lawsuit of its kind in the US. Under this deal, thousands of plaintiffs would receive about $275,000 each.[1]

[1]   Lorenzetti, Laura. “Takeda’s ready to shell out $2.2 billion to settle Actos drug cases” Fortune, April 1, 2015. http://fortune.com/2015/04/01/takeda-diabetes-cancer/

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Complications & Side Effects of Actos

Unfortunately, Actos’ meteoric rise hides a shadow side. Epidemiological studies have recently uncovered a significant increase in bladder cancer for patients who take Actos for two years or more.6

Takeda provided no prior warning for this potentially-deadly side-effect. In June of 2011, following these revelations, the French Agency for the Safety of Health Products withdrew the drug for use in France. Germany’s Federal Institute for Drugs and Medical Devices responded the following day, warning doctors not to prescribe Actos to new patients until more investigation had clarified its risks.

Although the FDA hasn’t banned the use of Actos in the US, they issued a warning and required Takeda to include a notice on their label stating that using the drug for over a year may be associated with increased risk of bladder cancer. They recommend not prescribing the drug to anyone with bladder cancer history.7

There are a number of other serious side effects associated with Actos, such as congestive heart failure, an increased number of bone fractures in females, macular edema, and possible liver failure. The drug hasn’t been approved for use by those under the age of 18, or those who are pregnant or breastfeeding. It also should never be used by people with type-1 diabetes or diabetic ketoacidosis, since it may exacerbate these conditions.8

Thousands of people who took Actos and developed bladder cancer have filed lawsuits against Takeda Pharmaceuticals and Eli Lilly. Following several cases where plaintiffs were awarded sizeable amounts in damages, Takeda has recently offered a $2.2 billion dollar settlement for those who claim they were harmed by the company’s failure to warn of the drug’s risks.

  • Bladder Cancer
  • Congestive Heart Failure
  • Bone Fractures in Females,
  • Macular Edema
  • Possible Liver Failure.

Complications and Side-Effects

Patients who take Actos to treat their type-2 diabetes can face a number of side effects, some of which are so serious that in 2012 Consumer Reports advised diabetics to take Actos “only as a last resort”[1]

Bladder Cancer

One major concern with Actos users is the risk of cancerous bladder tumors. In a study presented by the prestigious British Medical Journal in May 2012 which brought together a large group of patients with type-2 diabetes and followed up on them for 22 years, it was found that those who take Actos for an extended period have an 83% higher risk of developing bladder cancer. Study authors note particular concern that using Actos or its generic equivalent “seems to increase the risk over a relatively short duration of use — that is, after two years”.[2]

But even before this thorough study, the possibility of this risk had been known to Takeda for years. Several studies had linked bladder cancer with Actos — including the preclinical trials conducted by Takeda itself prior to marketing the drug. In their animal studies, they found that rats receiving the drug were more likely to suffer from bladder cancer.[3] The FDA notes two additional studies which have found a higher rate of bladder cancer among Actos users. They are currently requiring Takeda to undertake a ten-year study of the drug’s cancer risks, which is still underway. Interim analysis of the study has already shown a 40% increase in bladder cancer risks.[4]

If you have taken Actos, you may have increased risk for bladder cancer, particularly if you have taken the drug for more than two years. According to the Mayo Clinic, symptoms of bladder cancer include:

 

  • Blood in urine: this may make urine appear dark yellow, bright red, or cola colored. Urine may also appear normal, with blood detectable by microscopic examination.
  • Frequent urination.
  • Pain when urinating.
  • Back pain.
  • Pelvic pain.[5]

 

If you are experiencing any of these symptoms, make an appointment with your doctor. If you believe there is a link between your use of Actos and a bladder cancer diagnosis, you may be eligible to seek compensation from the drug manufacturers and marketers.

Congestive Heart Failure

Another serious condition to threaten users of Actos is congestive heart failure, a chronic condition in which the heart weakens and stops pumping blood as well as it should. It’s the leading cause of hospitalization in people over 65 years old.

Actos became popular after a chemically similar drug was pulled from the market due to concerns over congestive heart failure. Though it appears to not be as dangerous as its predecessor, Actos has a black-box warning for this side effect, and patients with a history of heart failure should either avoid the drug or be monitored by their medical team while they’re taking it.

Symptoms of congestive heart failure include:

  • Congested lungs, which causes shortness of breath due to fluid in the lungs and difficulty breathing while lying down. It may include a dry, hacking cough.
  • Fluid retention: as less blood flows to the kidneys, fluid gets backed up in the body. This can result in swollen limbs or abdomen (edema) and weight gain. It may also be accompanied with more frequent urination at night, nausea, bloating, and loss of appetite.
  • Dizziness, fatigue, and weakness, as less blood flows to the organs and brain.
  • Rapid or irregular pulse, as the heart beats faster to try to make up for inefficient pumping.[6]

 

Bone Fractures

Women who take Actos may double their risk of breaking bones, especially in the forearms, hands, lower legs, and feet.[7]

Liver Failure

Following the manufacture and marketing of the drug, patients taking Actos have reported cases of liver failure, some of which have been fatal. As there has not been conclusive evidence either of the drug’s danger or safety regarding the user’s liver, the FDA urges caution in using it. Liver function tests should be done prior to beginning the Actos, and doctors should regularly monitor the patient for signs of liver damage. Symptoms may include:

  • Yellowing of the skin or eyes (jaundice)
  • Pain in the upper right quadrant of the abdomen
  • Swelling of abdomen
  • Nausea
  • Vomiting
  • Fatigue
  • Dark urine[8]

[1]   Belfort, Renata et al. “A Placebo-Controlled Trial of Pioglitazone in Subjects with Nonalcoholic Steatohepatitis” The New England Journal of Medicine 355 (2006): 2297-2307. http://www.nejm.org/doi/full/10.1056/NEJMoa060326

[2]   FDA prescribing label for Actos. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf

[3]   Summary of Financial Statements [Japan GAAP] (Consolidated): Financial Results for the Fiscal Year Ended March 31, 2013, Takeda Pharmaceutical Company Limited. http://www.takeda.com/investor-information/files/qr2012_full_f_en.pdf

[4]   Harris, Gardiner. “Research Ties Diabetes Drug to Heart Woes,” The New York Times. Feb 19, 2010. http://www.nytimes.com/2010/02/20/health/policy/20avandia.html

[5]   Feeley, Jef. “Takeda Jury Can Hear Claims Over Destroyed Actos Files” BloombergBusiness. Jan 30, 2014. http://www.bloomberg.com/news/articles/2014-01-30/takeda-jury-can-hear-claims-over-destroyed-actos-files

[6]   Jouan, Anne. “L’antidiabétique Actos retiré du marché” Le Figaro. June 9, 2011. http://www.lefigaro.fr/flash-actu/2011/06/09/97001-20110609FILWWW00505-info-le-figaro-lantidiabetique-actos-retire-du-marche.php

[7]   FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer. US Food and Drug Administration. June 15, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm259150.htm

[8]   FDA prescribing label for Actos. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf

[9]   Feeley, Jef. “Takeda Denies Actos Bladder-Cancer Link at First Trial” BloombergBusiness. April 16, 2013. http://www.bloomberg.com/news/articles/2013-04-16/takeda-denies-actos-bladder-cancer-link-at-first-trial

[10]   Feeley, Jef. “Takeda Jury Can Heart Claims Over Destroyed Actos Files” BloombergBusiness Jan 30, 2014. http://www.bloomberg.com/news/articles/2014-01-30/takeda-jury-can-hear-claims-over-destroyed-actos-files

[11]          Moylan, Tom. “Jury Awards $9B in 1st MDL Actos Bladder Cancer Trial Against Takeda, Eli Lilly” LexisNexis Legal Newsroom. April 8, 2014. http://www.lexisnexis.com/legalnewsroom/litigation/b/litigation-blog/archive/2014/04/08/jury-awards-9b-in-1st-mdl-actos-bladder-cancer-trial-against-takeda-eli-lilly.aspx

[12]   Lorenzetti, Laura. “Takeda’s ready to shell out $2.2 billion to settle Actos drug cases” Fortune, April 1, 2015. http://fortune.com/2015/04/01/takeda-diabetes-cancer/

[13]   Mitchell, Steve. “New generic version of the diabetes drug Actos is one ‘bargain’ to avoid” Consumer Reports News. August 21, 2012. http://www.consumerreports.org/cro/news/2012/08/new-generic-version-of-the-diabetes-drug-actos-is-one-bargain-to-avoid/index.htm

[14]   Azoulay, Laurent et al. “The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study” BMJ 344: e3645 (April 2012). http://www.bmj.com/content/344/bmj.e3645

[15]   FDA prescribing label for Actos. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf

[16]   FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer. US Food and Drug Administration. June 15, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm259150.htm

[17]   Bladder cancer symptoms. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/bladder-cancer/basics/symptoms/con-20027606

[18]   Heart Disease Health Center: Heart Disease and Congestive Heart Failure. WebMD. http://www.webmd.com/heart-disease/guide-heart-failure

[19]          FDA prescribing label for Actos. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf