Actos Discussions Part 2: Dangers of the Drug

By Independent Staff Writer

Could Your Heart Failure Be Linked to Actos?
Links to higher heart disease rates have been associated with the use of Actos, and, in fact, Actos may cause as many heart problems as GlaxoSmithKline’s drug, Avandia. The American Heart Association reported that studies showed patients taking either diabetes drug were at least four times as likely to experience heart attacks, heart failure or even death. When a 2007 study on Avandia showed a 43 percent higher chance of heart attack, Actos quickly became the market leader. A subsequent study on both drugs showed that 602 Avandia users and 599 Actos users in the study suffered either a heart attack, heart failure or both, with 217 deaths in each group.  The latest study regarding Actos in the journal Lancet found the risk for heart failure greatest among those patients with a prior history of heart disease and heart failure, however overall the relative risk when taking Actos was as much as 72 percent higher than those not taking the drug. Both Glaxo and Takeda dispute the results of these negative studies, citing a study published in the Journal of the American Medical Association which suggests Actos might actually cut the risk of heart attack, stroke and death.

Link between Actos and Heart Failure
Actos is in a class of drugs known as thiazolidinediones, whose use has long been attributed to certain liver and cardiovascular health issues. A listed side effect of Actos includes the threat of congestive heart failure with the link between Actos and congestive heart failure being so undeniable that in 2007 the FDA escalated warnings regarding heart disease when taking the drug. Actos causes the body to retain excess fluid, leading to swelling and weight gain. This extra body fluid can worsen some heart problems, leading to heart failure or can actually cause heart problems.

When Actos causes swelling in the body, this swelling also occurs around the heart, rendering it unable to effectively pump blood throughout the body. As fluid builds up around the heart and lungs, it becomes more difficult for the heart to pump, causing it to become less and less efficient. This can lead to shortness of breath, trouble breathing when lying down, a feeling of excessive tiredness or an unusually rapid increase in weight. After an intense debate over the cardiovascular risks of Actos, the FDA agreed to surround the heart risk warnings on Actos with an emphatic black outline commonly known as a black box warning. This black box warning is the strongest FDA label change which can be added to any drug on the market.

Link Between Actos and Bladder Cancer
The FDA issued its safety announcement regarding the connection between using Actos for more than one year and the risk of bladder cancer on June 15, 2011. The bladder lies in the center of the lower part of the abdomen, and its primary purpose is to store urine prior to excreting it from the body. When cells in the bladder become cancerous, a tumor can form. Actos helps diabetics use their own insulin better by hitting at least two of the three main PPAR receptors known as the Gamma and Alpha receptors. The Gamma receptor works on glucose while the Alpha receptor affects cholesterol. Actos appears to have a higher affinity with the Alpha receptor which is why it does a good job on raising good cholesterol and lowering triglycerides.

It has been hypothesized that the way in which Actos reacts with these receptors may also be the reason it contributes to the risk of bladder cancer. Potential symptoms of bladder cancer include bloody urine, chronic and persistent infections of the bladder, a strong urge to urinate or pain and burning during urination. X-rays may reveal an abnormality in the bladder walls, or red blood cells found in the urine during lab tests. If the bladder is swelling, a biopsy may be done or a growth in the bladder could be discovered through a CT or MRI scan. Bladder cancer is typically treated with removal of the tumor, surgical removal of all or part of the bladder or with drugs which help the immune system fight the cancer.

Could Actos Damage Your Liver or Kidneys?
In addition to potentially damaging the heart and bladder, Actos may also be linked to rhabdomyolysis which occurs when muscle fibers rapidly bread down releasing proteins and myoglobin into the blood stream. Myoglobin can be toxic to the kidneys, leading to the development of rhabdomyolysis. Symptoms of this serious kidney disease include muscle pain or tenderness, stiffness or weakness in the joints and dark-colored urine. Actos has also been documented to cause elevated liver enzymes, a precursor to liver damage. Anyone who is considering taking Actos should have their liver enzymes tested before they start taking the drug, and should periodically monitor the liver enzymes while on Actos.

Actos® Adverse Effects

Actos® Adverse Effects

Many of us would be very surprised to find that a drug can be approved by the FDA yet still have serious—and undisclosed—side effects. The drug Actos, used in the treatment of Type 2 diabetes, is one such drug. Actos works by decreasing the body’s resistance to insulin as a way of controlling blood sugar levels. Actos is currently being used by millions of people across the globe, with sales jumping from around $2.9 billion in 2006 to over $4.3 billion in 2010. Actos has often been prescribed in place of the drug Avandia, which was found to carry significant risks of heart disease and possibly even death in 2007. Actos, which is manufactured by the Japanese pharmaceutical giant Takeda Pharmaceuticals, has recently fallen under scrutiny as well as studies have linked it to an increased risk of bladder cancer as well as correlating it to other serious diseases such as heart attack, stroke and liver failure.

“Minor” Side Effects of Actos
The truth is, all prescription medicines as well as most over-the-counter medications, carry some risk of adverse effects. Fortunately the incidence of serious side effects is rare and for the most part the majority of people have either no side effects or relatively minor ones. Minor side effects associated with Actos include flu-like symptoms, headaches, toothache, sore throat or sinus pain and weight gain. More serious side effects which should prompt the user to seek medical attention include an allergic reaction which includes difficulty breathing or chest tightness, blurry vision, symptoms of heart or liver failure including breathing difficulties, a sudden gain in weight, stomach pains, dark urine, jaundice or vomiting, low blood sugar symptoms such as tremors, anxiety or chills, severe and unusual bone pain and total exhaustion along with feeling weak and shaky.

Actos® and Congestive Heart Failure

Actos® and Congestive Heart Failure

The drug Actos, also known as pioglitazone is marketed by Takeda Pharmaceuticals and Eli Lilly for the treatment of Type 2 diabetes. The drug was approved in 1999, and although the manufacturer touts it as a miracle drug which has reduced the number of diabetes cases by as much as 70%, the side effects may far outweigh the benefits. A study done in 2003 by the Mayo Clinic definitively linked Actos to swelling in the feet, lung fluid retention, shortness of breath and congestive heart failure. The most recent studies have strongly indicated that Actos may also be responsible for a number of incidences of bladder cancer in those who have taken the drug in higher dosages or for longer than twelve months.

The American Diabetes Association presented a research report at a meeting in San Diego this past June which reported that Actos enhanced the risk of macular edema by as much as six times, causing thickening and swelling of the retina and leading to blindness. Another study which was reported in the American Heart Association Journal in August, 2010, associated Actos with an increased risk of death due to congestive heart failure. Although the FDA had mandated a black box warning for Actos regarding possible heart failure risks in 2007, the warnings became even more stringent this past June.

Actos® European Recall and FDA Stance

Actos® European Recall and FDA Stance

A wave of recent studies which definitively link the prescription drug Actos—prescribed for Type 2 diabetes—to bladder cancer gives a fairly clear indication that Takeda Pharmaceuticals may soon be flooded with Actos lawsuits. August, 2011, saw the first Actos lawsuit filed by a 54-year old woman from Pennsylvania who had taken Actos for over a decade, then was diagnosed with bladder cancer. It is likely this particular victim may end up having her bladder removed and be subject to chemotherapy treatments due to the unexpected and severe side effects of Actos. Although the FDA has made substantial changes in labeling for Actos, they have refused to go as far out on the limb as other countries who have issued recalls of the drug.

France’s Medical Regulatory Agency made the decision to recall Actos once the serious side effects became known. Some 230,000 people regularly take Actos in France, and the possibility of an increase in bladder cancer was felt to be too great to allow patients to continue to take the drug. Soon after, Germany’s health regulators advised physicians to stop prescribing Actos for their patients with Type 2 diabetes due to the potentially dangerous side effects of the drug. These recalls and prohibitions were made after the European Medicines Agency conducted its own study of drugs which contained pioglitazone.