08 February 2006 - IMPORTANT Trasylol Safety Information
February, 2006 Dear U.S. Healthcare Professional: Bayer Pharmaceuticals Corporation (Bayer) would like to inform you that Bayer and the U.S. Food and Drug Administration (FDA) are evaluating recent reports published in the medical literature concerning Trasylol® (aprotinin injection) ) and the occurrence of serious adverse events among patients undergoing cardiac surgery. A study entitled, “The Risk Associated with Aprotinin in Cardiac Surgery” by Mangano et al., was published in the New England Journal of Medicine, (Mangano D, Tudor J, Dietzel C. N Eng J Med, 2006 (354) :353-65. www.nejm.org). The publication describes the findings from an observational study of 4,374 patients (1,295 treated with aprotinin) scheduled for coronary artery bypass graft (CABG) surgery in multiple centers in multiple countries. Patients received either no therapy for blood loss, or a drug therapy intended to reduce blood loss (aprotinin, aminocaproic acid, tranexamic acid). The NEJM publication reported an association of aprotinin with increased risk of cardiovascular events (myocardial infarction or heart failure), cerebrovascular events such as stroke, encephalopathy or coma, and renal dysfunction or failure in patients undergoing CABG surgery. Patients were not randomized to these treatments. Instead, choice of study drug (or no treatment) was at physician discretion. Patients receiving aprotinin may have been at a higher risk to begin with for developing renal failure, myocardial infarction, heart failure or stroke compared to patients receiving no treatment or treatment with another drug intended to decrease bleeding. This possibility prevents a direct assessment of whether aprotinin altered the risk for serious adverse events. To try to adjust for known differences between the treatment groups, the study authors used statistical procedures (multivariable logistic regression and propensity score adjustments). A study entitled, “A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery” by Karkouti et al. has been published in the journal Transfusion (Karkouti K, Beattie W, Dattilo K, McCluskey S, Ghannam M, Hamdy A, et al., Transfusion, on-line edition, 1/20/06. www.blackwellpublishing.com/journal.asp?ref=0041-1132). This was also an observational study that used statistical methodology to compare outcomes from patients undergoing CABG. Like the NEJM study, the patients in this study received, at physician discretion, either Trasylol or another drug intended to decrease the risk for perioperative bleeding. The study in Transfusion has some of the same limitations as the NEJM publication. The study suggested that Trasylol administration increased the risk for renal dysfunction or failure. Renal dysfunction and renal failure have previously been reported in patients receiving Trasylol and are reflected in the current FDA approved labeling for Trasylol. The study by Karkouti et al. did not find an increased rate of cardiovascular or cerebrovascular events in Trasylol-treated patients and reported comparable mortality rates between the control treatment group and the Trasylol group. The FDA will review the NEJM and Transfusion reports, data supplied by Bayer and the authors of the studies, other reports in the literature as well as reports submitted to the FDA through the MedWatch program, to determine if any actions are warranted. Bayer welcomes this evaluation and the FDA’s accompanying guidance to physicians and patients. While the evaluation of these published reports and other relevant data continues, the FDA has provided guidance for physicians and patients in the form of an Alert for Healthcare Professionals and a Public Health Advisory concerning Trasylol. These documents and questions and answers related to this issue are posted on the FDA’s website at www.fda.gov. The FDA’s guidance includes a recommendation that physicians carefully monitor patients receiving Trasylol for the occurrence of adverse events particularly related to the kidneys, heart, or central nervous system and promptly report any events to Bayer or the FDA’s MedWatch program. The FDA also suggests that while the evaluation continues, physicians should consider limiting Trasylol use to situations where the clinical benefit of reduced blood loss is essential for medical management of the patient and outweighs potential risks. Bayer supports these actions by the FDA. We have been working and will continue to work closely with the FDA and other regulatory authorities in countries where Trasylol is marketed to address questions regarding product safety. We share the company’s data on Trasylol with regulatory authorities on an ongoing basis and welcome their evaluation of these published reports. Bayer believes that Trasylol is a safe and effective treatment when used in accordance with the product labeling. The current U.S. Prescribing Information for Trasylol is available on www.trasylol.com. If you wish to request further information, please contact Bayer Pharmaceuticals Corporation Clinical Communications at 1-800-288-8371. Sincerely, Paul MacCarthy, MD, FRCPI
Vice President, Medical Affairs
Bayer Pharmaceuticals Corporation
