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

The U.S. Food and Drug Administration (FDA) advised that GlaxoSmithKline, Avandia’s maker, agreed to add the new warning to the existing black box warning. But, despite the revision, the FDA will not withdraw Avandia from the market, claiming that evidence for increased heart attack is inconclusive and does not appear to be higher in Avandia than other type 2 diabetes treatments. In the meantime, the FDA asked GlaxoSmithKline to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results will not be available until 2014. Patient advocates and FDA critics consider the black box warning a weak response to Avandia’s safety issues and have requested Avandia be pulled from the market.

Avandia breaks down the body’s resistance to insulin but has long been known to cause fluid retention, a major risk factor for congestive heart failure. Evidence does not indicate Avandia and other oral anti-diabetes drugs-thiazolidinediones-prevent cardiovascular risk as a result of reducing blood sugar.

The American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated with thiazolidedione and rosiglitazone (Avandia) and may result in increased risk of myocardial infarctions. In October, the US Department of Veterans Affairs (VA) announced it was dropping Avandia from its prescription drug formulary stating their review concluded that, in some, Avandia did not afford the same margin of safety as other diabetes medications. The VA accounted for nearly 10-percent of Avandia’s US sales.

In November, Health Canada sent a letter to Canadian health professionals advising Avandia could no longer be prescribed as monotherapy for type 2 diabetes or in combination with sulfonylurea. In May, research based on 42 Avandia studies confirmed a 43-percent increased risk of heart attack among patients taking the drug. In August, Avandia’s warning label was changed to warn that Avandia and others in its class might worsen heart failure.

A Congressional Committee Report found that company executives made a concerted effort to intimidate a diabetes expert into keeping quiet about Avandia’s safety problems, alleging that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved. An internal government memo dated July 16, 2002 analyzed 47 early FDA reports of patients who went into heart failure and required hospitalization while taking Avandia. The report contained warnings from Federal investigators that Avandia might cause heart failure.

Over six million Americans have used the drug to treat adult-onset, or type 2, diabetes and the concern about Avandia is nothing new. The association between Avandia and increased heart failure risk has been known since 1999 when the drug was first approved.

Avandia was Glaxo’s second most popular drug in 2006, with sales of $3.3 billion. Sales have plummeted since publication of evidence linking Avandia with increased risk of heart attack and failure.

November 29th, 2007 by Staff with NewsInferno.com

SOURCE: Avandia Recall › Avandia heart attack controversy results in black box warning

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