Search Results for: thiazolidinediones

What is Avandia?

Avandia, also known as rosiglitazone, is a drug manufactured and marketed by pharmaceutical giant GlaxoSmithKline (GSK). The drug is used to treat diabetes and is a member of a class of drugs known as thiazolidinediones. These drugs reduce insulin resistance in muscle and fat as well as reduce glucose produced by the liver. Other drugs in this class include Pioglitazone, also known as Actos (marketed and manufactured by Takeda Pharmaceuticals) and Troglitazone (manufactured in the USA by Parke-Davis).

Avandia side effects

In 2007, a meta-analysis was published in the New England Journal of Medicine. A meta-analysis combines data from a number of related studies in an attempt to discover trends that would not otherwise be detectable in individual studies.

The authors of the meta-analysis reported that patients taking Avandia were at a 43% increased risk of myocardial infarction and 64% increased risk of death from cardiovascular causes.

The authors concluded that both patients and health care providers should take into account the increased risk of adverse events associated with the drug. One of the authors, Steven Nissen, was financially supported by a consortium of GSK’s competitors (including AstraZeneca, Parke-Davis, Pfizer, Daichi Sanyo [maker of Troglitazone in Japan] and others).

Following an FDA investigation of the drug, it was concluded that it did not cause a significant increase in heart attacks and the drug was allowed to remain on the market.

Avandia lawsuits

GSK faced 5,500 claims alleging that the company concealed the heart attack risk from the consumers and health professionals. The company agreed to settle the lawsuits on the eve of the first trial and paid claims averaging $46,000 each. An analyst at UBS AG in London commented that Glaxo would have been forced to pay as much as $1 million per case if Avandia had been definitely proven to cause heart attacks.

Read more about Avandia legal claims

References

Nissen SE and Wolski K, “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes.” New England Journal of Medicine 356:24 (2007).

“GlaxoSmithKline settles Avandia lawsuit on eve of trial,” The Telegraph, January 31, 2011 – URL: http://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/8293684/GlaxoSmithKline-settles-Avandia-lawsuit-on-eve-of-trial.html

“Glaxo Said to Pay More Than $250 Million to Settle Avandia Death Lawsuits,” Jef Feeley, Bloomberg, February 7, 2011 – URL: http://www.bloomberg.com/news/2011-02-07/glaxo-said-to-pay-more-than-250-million-to-settle-avandia-death-lawsuits.html

Common Diabetes Drug Linked to Site-Threatening Vision Complications

A June 2012 study published in the Archives of Internal Medicine (http://jamanetwork.com), presents strong evidence of a link between a popular treatment option for type 2 diabetes and a serious vision condition known as diabetic macular edema (DME).

The class of drugs, known as thiazolidinediones, has been recommended by the American Diabetes Association (ADA)(http://www.diabetes.org/) as a second-line therapy for treatment of patients with type 2 diabetes mellitus. In order to achieve target levels of glycemic control, the drug is often used in combination therapy with insulin or other oral agents. Popular formulations include Actos and Avandia. Previous case reports and analyses have highlighted the need for further investigation as increased incidents of DME, as well as other adverse effects such as bone fractures and bladder cancer, were reported in patients using this class of drug.

Diabetes and Eye SightDiabetic macular edema is a condition affecting the retina of the eye. Retinopathy, a common condition for people with diabetes, is caused by a swelling of the capillaries around the eye. Retinopathy can go undetected for some time as vision is not initially changed or affected. Yet, stemming from untreated retinopathy, the more serious condition of DME occurs when the weakened capillaries allow fluid to leak into the focusing part of the eye, or the macula. The macula then swells, and vision becomes blurred and eventually is lost entirely. Untreated, DME is a chronic, site-threatening condition.

This most recent study presents compelling evidence of the link between thiazolidinediones and DME. The authors reviewed the medical records of over 100,000 patients as they progressed through treatment for type 2 diabetes over a period of 10 years. The study summarizes that there does exist an increased risk for development of diabetic macular edema in diabetes patients who are taking thiazolidinediones. Furthermore, the risk is greater for those also using insulin as a combination therapy option. Risk also increases with the duration of the treatment.

Unfortunately, the early stages of DME often go undetected for long periods as many patients do not experience symptoms before the damage is done. A change in vision may not be noticed until the retina is already damaged beyond repair. In fact, in patients with type 2 diabetes, DME is the now the leading cause of blindness. For this reason, the study stresses the now increased importance of routine screening for DME in type 2 diabetes patients using thiazolidinediones.

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Actos® and the FDA

Actos®, the brand name of the diabetes drug pioglitazone is manufactured and distributed by Takeda Pharmaceuticals. Since the drug’s introduction by Takeda in 1999, the company has been forced to revise its official usage and recommendation labels several times by the U.S. Food and Drug Administration (FDA). Changes to the label were mandated by the FDA after reports from several studies showed that pioglitazone use may be linked to an increased risk of developing congestive heart failure and/or bladder cancer. The following drugs other than Actos® contain pioglitazone and are included in the FDA actions: Actoplus Met and Duetact.

Actos® and Congestive Heart Failure

The first FDA revision to the official prescribing information for Actos® and other pioglitazone-based drugs was made in August 2007. The revision includes a new boxed warning, updated warnings, and updated precautions and contraindications all related to the increased risk of congestive heart failure. The warnings came about after several reports of heart failure in patients taking Actos®. The increased risk of heart failure is thought to be related to one or more recognized side effects of the drug: fluid retention, edema and weight gain.

Patient Information – Healthcare practitioners and physicians are warned that all patients must be informed that Actos® may cause fluid retention, which can lead to congestive heart failure. Patients are also to be advised that any symptoms of congestive heart failure should be immediately reported to a physician. These symptoms include fluid retention, edema, rapid weight gain, fatigue, and difficulty breathing.

Recommendations – The FDA has determined that Actos® and all drugs in the classification of thiazolidinediones may cause or worsen incidents of congestive heart failure. Patients with a history of heart failure should not be prescribed Actos®. Physicians should monitor patients after prescribing or changing the dose of Actos®. If symptoms of heart failure develop, appropriate steps should be taken, including the consideration of discontinuing Actos® treatment.

Actos® and Bladder Cancer

The second FDA revision to the official prescribing information for Actos® did not occur until August 2011, but notices concerning a possible safety issue concerning an increased risk of bladder cancer were issued in September 2010. The notice was made after preliminary reports from the halfway mark of a 10-year study on Actos® and bladder cancer were analyzed by the FDA.

The FDA announced in June 2011 that the safety notice would be upgraded to an official warning and information about the risk of developing bladder cancer would be added to the official label for Actos®. The upgrade of the notice to a warning was made after further analysis of the preliminary reports from the 10-year study and analysis of a study in France that corroborated the evidence. Based on the French study, France has suspended the use of pioglitazone and Germany has issued a stern recommendation advising physicians against its use.

Patient Information – Patients should be informed of an increased risk in developing bladder cancer due to taking Actos®. Patients should not take Actos® if they are currently being treated for bladder cancer or have a history of bladder cancer. A physician should be notified in the event of any symptoms of bladder cancer. These symptoms may include blood in the urine, discolored urine, frequent or urgent need to urinate, pain while urinating, pain in the lower back, and abdominal pain.

Recommendations: Physicians are warned not to prescribe Actos® to patients with bladder cancer and discontinue use if bladder cancer develops while taking Actos®. Actos® must be used cautiously for patients with a history of bladder cancer, and the benefits of Actos® should outweigh the risks of a recurrence of the cancer. Adverse events in patients taking Actos® should be reported to the FDA through the MedWatch program.

FDA Warns of Actos Bladder Cancer Risk

FDA Warns of Actos Bladder Cancer RiskAfter nations in the European Union performed several studies on Takeda Pharmaceutical's diabetes drug Actos, leading to suspension of the medicine in France and Germany, the U.S. Food and Drug Administration came out saying the popular drug may increase the risk of bladder cancer if used for more than a year, HealthDay reported.

According to the news source, Actos belongs to a class of medicines called thiazolidinediones, the same class in which Avandia is found. Avandia was removed from pharmacy shelves in America, after it was linked to an increased risk of heart attack in May of 2011.

The FDA has ordered that the new cancer warning must appear on the labeling of Actos.

Actos is used as a means to control blood sugar in diabetics and is often used in combination with metformin and glimepiride. It has been a very popular choice for doctors to prescribe, as more than 2 million patients were taking Actos in 2010.

The FDA decided to create the new label for the drug after reviewing data from an ongoing study that found patients who took Actos for long periods at high doses had an increased risk of bladder cancer, HealthDay stated.

Another study involved more than 193,000 diabetic patients who had been taking Actos for two years on average.

"Compared to never being exposed to pioglitazone, a duration of pioglitazone therapy longer than 12 months was associated with a 40 percent increase in risk [for bladder cancer]," the agency said in response to the large study.

The FDA also acknowledged the French study that prompted health officials in the country to pull Actos from the shelves, stating that the study accurately outlined a dose-response effect in which bladder cancer risks rose after patients had taken the drug for more than one year, according to HealthDay.

Now, the FDA is urging doctors to steer away from prescribing Actos to patients who already have bladder cancer and to use caution when prescribing to patients who have had bladder cancer in the past. The agency warns that diabetic patients should seriously weigh the "benefits of blood sugar control with pioglitazone against the unknown risks for cancer recurrence."

The FDA says that those who take diabetes medicines such as Actos should report any symptoms of bladder cancer, which include blood in the urine, abdominal pain, incontinence and weight loss, according to the National Library of Medicine.
 

Popular Diabetes Drug Actos Suspended in European Countries

Popular Diabetes Drug Actos Suspended in European CountriesAfter Takeda Pharmaceutical Co.’s best selling diabetes drug Actos was shown to be linked to an increased risk of bladder cancer in a French study, the drug was suspended in France and Germany, Bloomberg reported.

According to the news source, the French drug regulator known as Afssaps said that patients should not immediately stop taking the drug without talking to their doctors, but that physicians should cease to prescribe the drug following a meeting that weighed the medicine’s risks.

The mega-selling drug Actos, known also as pioglitazone, was responsible for Takeda’s massive report of $4.8 billion last year and made up 27 percent of Takeda’s revenue. The drug appeared in Europe in 2000 and was said to be an alternative treatment to metformin, which had been the standard prescription until 2000. The French drug regulator estimates that about 230,000 people were prescribed Actos throughout the country, the media outlet stated.

The European Medicines Agency (EMA), which had already been eyeing Actos and researching its possible bladder cancer risks, began an examination of the results of the French study in order to further clarify findings.

Following the EMA’s inquiry into the harmful side effects of Actos, Germany joined France in suspending the drug for diabetes treatments, and recommended that the EMA suspend all marketing approval for the drug across all 27 nations of the European Union, the San Francisco Chronicle reported.

The news source states that American doctors are considering no longer prescribing thiazolidinediones, or TZD’s, in the wake of all the research done on its link to bladder cancer.

“I don’t think doctors are going to continue to prescribe TZD-class drugs, and as far as my practice is concerned, I will tell my patients to stop taking Actos,” Albert Levy, an endocrinologist at Mount Sinai in New York, told the Chronicle.