ACTOS Risks: What Diabetics Need to Know, Explained by Your ACTOS Injury Lawyers
What is ACTOS?
ACTOS is one of a class of drugs called thiazolidinediones that are used to treat patients with Type 2 diabetes mellitus.
- ACTOS (pioglitazone hydrochloride, Takeda)
- ACTOplusmet (pioglitazone HCI + metformin HCI, Takeda)
- ACTOplusmetXR (pioglitazone HCI + metformin HCI extended-release, Takeda)
- Duetact (pioglitazone HCI + glimepiride, Takeda)
How does ACTOS work?
ACTOS works by decreasing the body’s resistance to insulin, thus helping to control blood sugar levels. The drug is taken by mouth, in pill form, usually once a day, with or without food.
Who is likely to be prescribed ACTOS?
ACTOS is not used for Type 1 diabetes –where the body does not produce any insulin of its own – or for a related condition called diabetes ketoacidosis. But ACTOS has become a critical part of the health maintenance regimen of millions of people with Type 2 diabetes.
What are the most recently disclosed side effects of ACTOS?
A recent Northern California study of 193,000 diabetic patients with Type 2 diabetes found that diabetics who took ACTOS had a 40% higher risk of developing bladder cancer than a control group.
ACTOS was approved by the FDA in July 1999. Prior to the public release of this study in 2011, there was no disclosed cancer warning in the ACTOS labeling information or the Patient Medication Guide.
Here is a summary of recent safety alerts for ACTOS:
- On September 17, 2010, the FDA issued a Drug Safety Communication associating ACTOS with an increased risk of bladder cancer among patients exposed to the highest cumulative dose of ACTOS and the longest exposure to ACTOS. However, the FDA concluded that “findings from studies in animals and humans suggest this is a potential safety risk that needs further study.” Healthcare professionals and patients were advised to continue to follow recommendations in the ACTOS drug warning label.
- In June 2011, a study by Dr. Carlo Piccinni and others with the University of Bologna was published in Diabetes Care. This article, “Assessing the Association of Pioglitazone Use and Bladder Cancer through Drug Adverse Event Reporting”, reflected Dr. Piccinni’s finding that of 93 bladder cancer cases reported between 2004 and 2009 by patients with diabetes, one-third of these patients were being treated with pioglitazone (ACTOS).
- On June 15, 2011, the FDA issued a Drug Safety Communication based on the agency’s review of data from a planned five-year interim analysis of an ongoing, ten-year observational cohort study, as well as a nested case-control study, among patients with diabetes mellitus (Type 2) who are members of the Kaiser Permanente Northern California health plan. The study involved review of data collected from January 1, 1997, through April 20, 2008. Analysis indicated that among those taking ACTOS for more than a year (30,173 patients), the risk of bladder cancer increased 40% over the risk of bladder cancer in patients who had never taken ACTOS. The FDA also noted its awareness of a retrospective cohort study of data collected between 2006 and 2009 from the French National Health Insurance Plan, which included 1.5 million patients with diabetes. This study showed a statistically significant increase in the risk of bladder cancer in patients exposed to ACTOS, compared to patients who used other anti-diabetic drugs. Similar to findings of the Kaiser Permanente study, the French study found that increases were related to higher doses and longer use of ACTOS. France and Germany immediately suspended the use of ACTOS on the basis of the French study results. ACTOS is scheduled to be recalled in New Zealand, as well.
I’ve heard ACTOS also causes Macular Edema and blindness?
In addition to the alarming news about risk of bladder cancer, a new study from the American Diabetes Association suggests that ACTOS and Avandia (rosiglitazone), a similar drug, are linked to development of macular edema. Macular edema is swelling of a very small area at the center of the retina, which can lead to loss of vision or blindness. This study indicates that patients who use ACTOS and Avandia are from three to six times more likely to suffer macular edema than those who do not take these drugs.
The results of this startling study were announced at a meeting of the American Diabetes Association in San Diego, California in June 2011. The study showed that ACTOS and Avandia raise the risk of macular edema and can lead to blindness. Dr. Richard Donnelly, a medical scientist at the University of Nottingham, concluded that patients at high risk of sight-threatening diabetic macular edema (DME) should not take any of the class of insulin-sensitizing drugs (thiazolidinediones) that includes ACTOS and Avandia.
For many years, Avandia (rosiglitazone) has been the subject of reports of safety issues, including increased risk of heart attacks, strokes, and congestive heart failure. Now banned in Europe, Avandia in the United States is restricted to very limited use by a small number of diabetic patients who cannot achieve control of their blood sugar with any other diabetes drugs. Avandia is scheduled to be pulled from all US retail pharmacies by November 2011.
ACTOS has been hailed as the safer alternative to Avandia, especially by its manufacturer, Takeda. This new evidence of links to macular edema and bladder cancer is particularly threatening to Takeda, as an estimated 2.3 million patients filled ACTOS prescriptions at outpatient retail pharmacies in 2010.
What other serious medical conditions can ACTOS cause?
ACTOS and its family of related drugs already have been linked to heart attacks, liver failure, strokes, and congestive heart failure, and can produce side effects that lead to other dangerous medical conditions.
Healthcare professionals warn Type 2 diabetes patients taking ACTOS to be alert to symptoms that, unless quickly evaluated and treated, can be life-threatening.
The first warning that ACTOS use can cause heart attacks, strokes, and congestive heart failure came from the FDA in August 2007. The agency issued an alert announcing revisions to the prescribing information, a new Boxed Warning, and updated Warnings, Precautions and Contraindications “to emphasize that pioglitazone (ACTOS) may cause or exacerbate heart failure, particularly in certain patient populations.” Similar warnings were also added to the Avandia warning label that year as well.
The revised Boxed Warning for ACTOS read:
WARNING: CONGESTIVE HEART FAILURE
- Thiazolidinediones, including ACTOS, cause or exacerbate congestive heart failure in some patients (see WARNINGS). After initiation of ACTOS, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea and/or edema). If these signs and symptoms develop, the heart failure should be managed according to the current standards of care. Furthermore, discontinuation or dose reduction of ACTOS must be considered.
- ACTOS is not recommended in patients with symptomatic heart failure. Initiation of ACTOS in patients with established NYHA Class III or IV heart failure is contraindicated (see CONTRAINDICATIONS and WARNINGS).
But this warning was just the beginning. In their study released in 2011, Dr. Donnelly and his colleagues at Nottingham University also concluded that ACTOS and Avandia are known to increase the likelihood of fluid in the lungs, called pulmonary edema, and swelling from fluid in the legs. Recent findings have implicated ACTOS in a litany of serious risks in addition to bladder cancer, macular edema, and heart failure. Current prescribing information required by the FDA warns healthcare professionals and patients about these risks associated with ACTOS:
- Bladder cancer
- Congestive heart failure (heart fails to pump sufficient blood to body)
- Macular edema (swelling of retina) or blindness
- Edema (fluid retention)
- Liver failure or hepatitis
- Fractures (especially in female patients)
- Hypoglycemia (low blood sugar)
- Heart attacks and other cardiac events
Healthcare professionals advise patients with diabetes Type 2 who are taking ACTOS to look for symptoms that could indicate any of the dangerous conditions listed above.
Warning signs of congestive heart failure include:
- Large weight gain in a short period of time
- Shortness of breath
- Swelling of arms, hands, feet, ankles, or lower legs
- Swelling or pain in stomach
- Waking up short of breath during the night
- Needing to sleep with extra pillows in order to breathe
- Frequent dry cough
What are the common side effects of ACTOS?
Common ACTOS side effects include cold symptoms, headache, muscle pain, tooth or mouth pain, and/or sore throat; patients should consult their doctor if these do not go away.
Other, more significant side effects require immediate attention because they could indicate a serious condition. These include:
- Loss of appetite
- Excessive tiredness
- Dark urine
- Yellowing of the skin or whites of the eyes
- Blurred vision
- Vision loss
- Increased tiredness