The group enumerated its concerns in a full petition, citing both safety and efficacy issues. Adverse events linked to Avandia and listed in the petition include liver failure, myocardial ischemia (increased risk of heart attack), congestive heart failure, macular edema (vision loss), anemia, and bone fractures.

One new analysis of the FDA’s Adverse Event Reporting System (AERS) data revealed that of 14 Avandia users who experienced kidney failure, 12 died.

“The evidence for this unique combination of toxicities is compounded by the accompanying lack of evidence of any clinical benefit, compared to other approved drugs for diabetes,” the petition states.

The petition also refers to statements released earlier by both the American Diabetes Association and the European Association for the Study of Diabetes advising against the use of Avandia given the availability of better options.

To support its claim, Public Citizen also included a graph highlighting the dwindling sales of Avandia from the first quarter of 2006 to the second quarter of 2008. 13.3 million Avandia prescriptions were written in 2006, yet only 4.6 million were written in the last year. Avandia prescriptions have declined steadily since late 2006.

“The FDA is in possession of clear, unequivocal evidence that (Avandia) causes a wide variety of toxicities,” Public Citizen said in its petition to the FDA.

Drugmaker GlaxoSmithKline issued a response to the petition on Friday, standing by Avandia.

“The safety of patients using our medicine is very important to us. On a continual basis, an external Hepatic Safety Board reviews any adverse event report received by GSK of liver failure, liver-related deaths and liver transplants for possible relationship to AVANDIA. As recently as July 2008, this panel of experts continued to endorse a favorable hepatic safety profile for AVANDIA,” the statement said.

Public Citizen is a nonprofit consumer advocacy organization representing more than 80,000 consumers in the U.S. It was founded in 1971 to “represent consumer interests to Congress, the executive branch, and the courts.”

SOURCE: Avandia Recall › Consumer watchdog urges immediate Avandia ban

Avandia’s heart attack link came to light when an analysis of 42 clinical trails published by the Cleveland Clinic in May showed that patients taking the drug had a 43% higher risk of having a heart attack. Just last month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks. However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues, and have called on GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

Now, it seems that Avandia side effects have reached the general public. That is made clear in a study conducted by scientists at the Institute for Clinical Evaluative Sciences in Toronto, Canada. Researchers there analyzed data for 159,026 older adults who were treated with at least one oral diabetes drug between 2002 and 2005 and were entered in an Ontario healthcare database.

The subjects were followed through March 2006. During an average follow-up period of 3.8 years, 7.9 percent of the patients were hospitalized for congestive heart failure, 7.9 percent were hospitalized for a heart attack, and 19 percent died, according to the researchers’ report in Journal of the American Medical Association. Further analysis revealed that the risks were largely confined to patients who were using Avandia, known generically as rosiglitazone.

The Canadian researchers wrote that their findings “provide evidence from a real-world setting and support data from clinical trials that the harms of thiazolidinediones may outweigh their benefits, even in patients without obvious…cardiovascular disease”.

This latest research does not bode well for Avandia. Earlier this month, pharmacy benefit managers HealthTrans and Prime Therapeutics announced that they would be dropping the controversial diabetes drug from their value-based prescription drug formularies as of January 1, 2008 because of safety concerns.

In October, the Department of Veterans Affairs (VA) announced that it was removing Avandia from its prescription drug formulary because of its heart attack risks. The VA said that it would still make Avandia available for patients who were already taking it and wanted to continue. But the decision means that patients not currently prescribed Avandia will not be able to get it through the VA in the future. Prior to its announcement, the VA accounted for about 8 percent of Avandia sales.

Avandia was once GlaxoSmithKline’s second-biggest selling drug, with worldwide revenue of $3.2 billion in 2006, but sales have plunged since May, with US sales down 48 percent in the third quarter from a year ago.

December 17th, 2007 by Staff with NewsInferno.com

SOURCE: Avandia Recall › Avandia heart attacks seen in general patient population

The Association announced on Tuesday that it was updating its “consensus statement” on the use of oral diabetes medications in light of the increased heart attack risks linked to some diabetes medicines, such as Avandia.

Avandia’s heart attack link came to light in May, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43% higher risk of having a heart attack. Earlier this month, the Food & Drug Administration (FDA) announced the addition of a long-awaited black box warning for Avandia’s increased risk of heart attacks.

However, many patient advocates and FDA critics thought the black box warning was a weak response to Avandia’s safety issues, and have called on both GlaxoSmithKline, the maker of Avandia, and the FDA to pull the drug from the market.

The American Diabetes Association’s revised consensus statement was formulated in cooperation with European Association for the Study of Diabetes. The statement reads in part: “New information suggests additional hazards associated with the use of either thiazolidedione, and rosiglitazone (Avandia) in particular may result in an increased frequency of myocardial infarctions. . .

We therefore recommend greater caution in using thiazolidediones, especially in patients at risk of, or with, congestive heart failure.”

The American Diabetes Association’s new Avandia stance is only the latest development that could hurt the drug’s sagging sales. In October, the United States Department of Veterans Affairs (VA) announced that it was dropping Avandia from its prescription drug formulary. In a statement announcing the move, the VA said that it had conducted its own review and concluded that, for some patients, Avandia did not afford the same margin of safety as other diabetes medications.

Prior to its announcement, the VA accounted for about 8% of Avandia’s sales in the United States. And in November, Health Canada sent a letter to Canadian health professionals informing them that Avandia could no longer be prescribed as monotherapy for type 2 diabetes, except when metformin use is contraindicated or not tolerated. Health Canada also withdrew its approval for Avandia to be used in combination with a sulfonylurea, except when metformin is contraindicated or not tolerated.

Last week, Glaxo got more bad news on the Avandia front when a Congressional Committee Report found that company executives made a concerted effort to intimidate Dr. John Buse, a diabetes expert, into keeping quiet about some of the Avandia’s safety problems. The report alleged that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.

November 27th, 2007

SOURCE: Avandia Recall › Avandia side effects prompt new caution from American Diabetes Association