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

In a floor statement placed in the Senate record, Sen. Charles Grassley also said that safety watchdogs within the federal Food and Drug Administration “several months ago” recommended a “black box” on the drug’s label, the strongest possible warning.It is the first confirmation that the FDA’s own analysis of Avandia shows a similar magnitude of heart attack risks, dangers that were first publicly raised in a medical journal report published earlier this week.

Grassley complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision.

“That’s a long time from now when you have millions of Americans taking this drug,” said the statement by the Iowa Republican. “Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem.”

The FDA has been under fire since Monday’s report came out, attacked by consumer advocates for dropping the ball on drug safety and for taking no stronger action in light of the new warning signs.

Avandia, sold by the British company GlaxoSmithKline PLC, is a blockbuster medication used to treat Type 2 diabetes, the most common form of the disease. More than 6 million people worldwide have taken the drug, whose U.S. sales topped $2.2 billion last year.

On Monday, an analysis led by Cleveland Clinic cardiology chief Dr. Steven Nissen of 42 separate studies on Avandia concluded that it raised the risk of heart attacks by 43 percent, compared to the rates among people taking no or other diabetes drugs. The analysis also indicated that Avandia might increase the risk of heart-related deaths.

GlaxoSmithKline strongly disputes the conclusions. Company officials said that while their own similar analysis suggested a 31 percent greater risk _ information it shared with the FDA as early as 2005 _ more rigorous, albeit smaller, individual studies did not show that.

Critics have accused the FDA of being lax in monitoring drug safety, and some members of Congress scheduled hearings and have subpoenaed key people to appear.

Grassley’s staff has been meeting with FDA staffers and others and gathering documents all week to investigate the issue, said Jill Kozeny, press officer for the Senate Finance Committee, of which Grassley is ranking member.

FDA spokeswoman Julie Zawisza confirmed Thursday the internal analysis that Grassley’s statement revealed, but added, “we have conflicting data” from individual studies, and therefore “are continuing to review the results of GSK’s ongoing trial to determine the actual risk.”

She said she could not discuss “ongoing regulatory matters” like the black box warning that Grassley’s statement says was urged months ago by the FDA’s Division of Drug Risk Evaluation.

As for the number of heart attacks possibly linked to the drug _ as many as 20 a day, Grassley contends _ Zawisza said: “A relationship between the drug and these deaths has not been established. We don’t have data to support such a conclusion.”

Any increase in heart attack risk is especially worrisome for diabetics because two-thirds of them die of heart problems.

About 1 million Americans are currently taking Avandia, which costs from $90 to $170 for a one-month supply. The FDA and diabetes experts are advising users of the medication to talk to their doctors and not to immediately discontinue the drug, which helps keep blood-sugar levels under control.

May 24th, 2007 by Marilynn Marchione with The Associated Press

SOURCE: Avandia Recall › FDA study said to show Avandia risk