Possible Avandia Recall: Liver Failure Cases May Tip Balance Of Risk vs. Benefit

October 2008 Public Citizen Petition Wants Glaxo's Diabetes Drug Banned Due To "New" Side Effect, Liver Toxicity

(Posted by Tom Lamb at DrugInjuryWatch.com)

On October 30, 2008 Public Citizen's Health Research Group (HRG) submitted a petition to the FDA requesting that GlaxoSmithKline's diabetes drug Avandia (rosiglitazone) be banned due to the drug's several serious side effects, including some newly found cases of liver failure.

According to this "Petition to Immediately Ban Diabetes Drug Rosiglitazone (AVANDIA) (HRG Publication #1848)":

Our petition is based on [Avandia]’s multiple, serious risks, including one just documented by our new analysis of 14 cases of liver failure, of which 12 resulted in death.

Besides the Avandia-induced liver failure, this Petition by Public Citizen's HRG pointed out several other serious side effects associated with Avandia, including:

Myocardial Ischemia: Three recent meta-analyses have demonstrated an increased risk of myocardial ischemia or myocardial infarction with [Avandia]. The approximate increase in the risk of heart attacks is 40%.

Congestive Heart Failure:... Several meta-analyses estimate the increased risk
to be approximately two-fold.

In this October 2008 document Public Citizen compared Avanida to Rezulin (troglitazone) when it comes to the risk for drug-induced liver failure, as is seen from the following excerpt from the Petition:

[Rezulin], a thiozolidinedione similar in structure to [Avandia], was approved for marketing by the FDA in March 1997, but was withdrawn from the market in March 2000 after 94 cases of [Rezulin]-induced liver failure, the majority of which were fatal, were reported.  Although the premarketing signal for hepatotoxicity with [Avandia] was not as strong as the signal with [Rezulin], one of the most hepatotoxic drugs ever approved by the FDA, several cases of [Avandia]-induced hepatotoxicity have been reported in the literature, and many more via the FDA Adverse Event Reporting System (AERS). [footnotes omitted]

Overall, according to Public Citizen -- taking into account the newly found cases of liver failure together with "the accompanying lack of evidence of any clinical benefit" when Avandia is compared to other diabetes drugs -- the time has come for the FDA to order an immediate Avandia recall.

In October 30, 2008 article, "Glaxo's Avandia Should Be Banned, Public Citizen Says (Update2)", Bloomberg reporter Justin Blum let us know the drug company's initial reaction:

Glaxo hasn't read the petition and "we do not believe there is a connection between liver toxicity and this medicine," according to an e-mail from company spokeswoman Mary Anne Rhyne. She said Avandia is safe "for appropriate type 2 diabetes patients, when used according to the label."

Previously, in the article "Mixed Reactions To Avandia's Revised Warning In November 2007 About Risk Of Heart Attacks"", we reported that in November 2007 the FDA issued a news release entitled "FDA Adds Boxed Warning for Heart-related Risks to Anti-Diabetes Drug Avandia", which carried the sub-heading "Agency says drug to remain on market, while safety assessment continues". 

One wonders, now, whether this apparent new link to liver toxicity will compel the FDA to ban Avandia as requested by Public Citizen.

P.S.  Late in the day on October 30 GlaxoSmithKline issued its formal response to the HRG Avandia Petition submitted to the FDA by means of this press release, "GSK Believes There Is No Liver Safety Issue With AVANDIA; Responds to Public Citizen Petition". 

The main point raised therein:

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.

There has been no word from the FDA about how long the agency will need to make a determination on the Avandia recall requested by Public Citizen.  (10/31/08)