December 2007 Safety labeling updates & new warnings: rosiglitazone, erythropoiesis-stimulating agents, aprotinin

Key Points

FDA has requested that new information about the potential for an increased risk of heart attacks be added to the boxed warning already included in the labeling information for rosiglitazone (Avandia, GlaxoSmithKline). The drug's manufacturer has agreed to add the information, which states that a meta-analysis demonstrated an increased risk of myocardial ischemic events with use of rosiglitazone compared primarily with placebo; several other studies comparing rosiglitazone with other oral antidiabetic drugs or placebo have not confirmed or excluded this risk. The boxed warning already includes information about the increased risk of heart failure with the use of rosiglitazone and other thiazolidinediones.

The labeling for erythropoiesis-stimulating agents (ESAs) (epoetin alfa, Procrit, Ortho Biotech; epoetin alfa, Epogen, Amgen; and darbepoetin alfa, Aranesp, Amgen) has been changed to add information regarding the safety and effectiveness of the drugs and to provide greater detail regarding their appropriate use. The changes include a warning stating that dosing to reach hemoglobin (Hb) levels <12 g/dL in patients with cancer does not exclude the risk of shortened survival and/or the risk of tumor progression. The labeling changes also include revisions to the dosing recommendations for anemic patients with chronic renal failure to include target Hb levels of 10 to 12 g/dL.

Marketing of aprotinin (Trasylol, Bayer) has been suspended because of concerns about a potential increased risk of death with use of the drug. In October 2007, the Data Safety Monitoring Board recommended that enrollment in a Canadian trial of aprotinin (Blood Conservation Using Antifibrinolytics: A Randomized Trial in a Cardiac Surgery Population [BART]) be stopped because of these risks. The study has been stopped, and the marketing suspension will continue until FDA completes a comprehensive review of the study.