Safety concerns about rosiglitizone (Avandia) (March 2010)

LWPES Members:

In the last 2 weeks, safety concerns about rosiglitizone (Avandia) have resurfaced due to reports from officials at the Food and Drug Administration (FDA), leaked to the popular press, that recommend that Avandia be removed from the market (1).  A congressional report was also recently released concluding that Avandia’s manufacturer, GlaxoSmithKline, had evidence of the cardiovascular risks that they did not report (2).  Since the press coverage, the FDA has formally released an announcement stating that the FDA is “reviewing [primary] data, submitted in August 2009, from a large, long-term clinical study on possible risks with the diabetes drug, Avandia (rosiglitazone)” (3).  The clinical study, Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes or RECORD was designed to evaluate the cardiovascular safety of rosiglitazone.  The FDA reports that it will release formal conclusions in regards to rosiglitazone at a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010. 
            The increased cardiovascular risk associated with rosiglitizone use first appeared in clinical trials published in 2007 and prompted the FDA to require GlaxoSmithKline to include a “black box warning” in the Avandia product labeling about the potential for myocardial ischemia and the potential to cause or exacerbate heart failure (4).  Multiple trials since that time have resulted in varying conclusions about the increased risk of myocardial ischemia and/or heart failure.  However, given the concern and the existence of alternatives, the American Diabetes Association and European Association for the Study of Diabetes advised against use of rosiglitizone in a consensus statement (5).  The cardiovascular risk of rosiglitazone in young patients is unknown.  
            Although rosiglitazone is rarely used in pediatric endocrine practice, the Drug and Therapeutics committee feels that its members should be aware of the above issues when making clinical decisions and in answering patients’ questions. 

1.  Harris, G.  Research ties diabetes drug to heart woes.  New York Times February 19, 2010.

2.   http://finance.senate.gov/press/Gpress/2010/prg022010b.pdf

3. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm201418.htm

4.  http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm143406.htm

5.  Nathan, DM et al.  Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.  Diabetologia 2009 52:17-30.