Questions and Answers on Aprotinin (marketed as Trasylol)
This product is not currently available for purchase in the U.S.
1. What is Trasylol and what is it used to treat?
Trasylol, or aprotinin, a product derived from bovine lung tissue, inhibits certain enzymes that increase the risk for bleeding. Trasylol administration aids the body's ability to prevent bleeding.
Patients undergoing coronary artery bypass grafting (CABG) using cardiopulmonary bypass may be at risk for bleeding complications due to prior use of anticoagulants or clinical conditions that predispose to bleeding. Trasylol is used to decrease this bleeding risk.
2. What is the concern regarding Trasylol?
A January 26, 2006 report in The New England Journal of Medicine suggests that Trasylol administration may increase the risk for serious side-effects among some patients undergoing CABG. This report describes the occurrence of serious kidney damage, heart attack (myocardial infarction) and stroke among CABG patients receiving Trasylol. More patients receiving Trasylol experienced these events than patients receiving either no medications intended to decrease blood loss or other medications intended to decrease blood loss.
Another recently published study has suggested that patients receiving Trasylol may be at higher risk for kidney damage. This report (published January 20, 2006 in the on-line edition of Transfusion) used methods similar to those used in The New England Journal of Medicine study but included a smaller number of patients.
3. Did the patients who developed these serious side-effects have other possible reasons to develop these reactions?
It is not known if the patients receiving Trasylol in The New England Journal of Medicine report were sicker and thus at higher risk prior to receiving Trasylol than the patients in the other study groups. The study report authors used statistical procedures to try to adjust for this consideration. In the Transfusion report, the patients seemed to be similar in both study groups.
4. Have other studies indicated problems with Trasylol?
In addition to the previously described studies, one additional study suggested that Trasylol administration may increase the risk for clot formation within coronary artery bypass grafts. In this study, patients receiving Trasylol were compared to those receiving a placebo. The study reported an increased rate of bypass graft closure for patients receiving Trasylol.
5. What are the strengths and limitations of The New England Journal of Medicine Report when compared to other reports?
The major strength of The New England Journal of Medicine study is the collection of information from a large number of patients who were managed according to common medical practice.
The major limitation of The New England Journal of Medicine study is that patients were not randomly assigned to any of the treatments (or to no treatment) for preventing bleeding. The treating physicians determined, based on their experience and judgment, whether to administer Trasylol, another drug to prevent bleeding, or no treatment. It is possible that the treating physicians may have chosen to administer Trasylol only to the sicker patients while the less sick patients received other products or no therapy to prevent bleeding. Consequently, the study outcomes may not truly indicate Trasylol side-effects. Instead, the study outcomes may indicate the seriousness of the underlying condition of the patients chosen to receive Trasylol. It is important to note that the study investigators used statistical analyses to try to correct for this limitation.
In clinical studies where the choice to use Trasylol or not was decided by chance alone, Trasylol administration was not associated with the detection of any increase in the risks for the serious side-effects described in The New England Journal of Medicine report. These types of studies were performed in order to rigorously detect the Trasylol effects. However, these studies also have limitations; for example, the patients enrolled in the study may not truly reflect all types of patients undergoing CABG and the other cardiovascular therapies used in the studies may differ from those routinely used in medical practice. These considerations are especially important when clinical advances may rapidly change the practice of medicine.
6. Was Trasylol responsible for the serious side-effects detected in The New England Journal of Medicine report?
The report suggests that Trasylol administration was associated with the serious side-effects. However, the limitations of the reported study require that the study findings be examined more closely.
7. Based on this report, why isn't FDA immediately removing this product from the market?
The findings from The New England Journal of Medicine report differ from the data submitted to the FDA in support of a marketing application. These other reports indicate that Trasylol has benefits that outweigh the risks associated with the product. The FDA is re-examining all these study findings in light of The New England Journal of Medicine report and other information.
8. Are other drugs available to decrease the risk for bleeding during CABG?
No other products are approved by FDA for use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing CABG with cardiopulmonary bypass. However, other products have been used by physicians in order to try to prevent bleeding during CABG. As described in The New England Journal of Medicine report, these other products include aminocaproic acid and tranexamic acid.
9. What actions will FDA take regarding these reports?
FDA is continuing to evaluate these reports, assessing other reports and working with the Trasylol manufacturer in order to determine if product labeling changes or other actions are necessary.
10. What information was known about serious side-effects prior to Trasylol approval?
In pre-marketing clinical studies, Trasylol was administered to approximately 2,000 patients undergoing CABG with cardiopulmonary bypass. In these studies, approximately 1,000 patients received a placebo instead of Trasylol. These studies found that Trasylol decreased the need for blood cell transfusion. The studies did not detect an increased risk for serious kidney or heart side-effects. Certain pre-marketing clinical studies showed that some patients may experience allergic-type reactions to Trasylol, especially patients who receive more than one Trasylol administration. These reactions, including hypersensitivity reactions and anaphylaxis, were rare among patients who received a single Trasylol administration (< 0.1%) but were more common among patients receiving repeat Trasylol administrations (approximately 5% in patients treated within 6 months of prior Trasylol exposure).
11. What should patients do regarding this new information?
Patients should be aware that the FDA is examining the safety and benefits of Trasylol, in light of the recent data and the evolving practice of medicine. Patients should discuss all major risks for CABG with their healthcare providers, including the risks for bleeding and the options to lessen the risk for bleeding.
12. What should healthcare providers do in response to this new information?
Healthcare providers should be aware that The New England Journal of Medicine report and another published report raise important questions regarding the on-going safety and benefits of Trasylol administration. FDA will provide healthcare workers and patients with the results of the on-going review of Trasylol effects as soon as possible.
13. What additional actions are likely to follow?
Once FDA completes its preliminary findings, multiple options are available to address the findings. These options include potential modifications of the product label, the performance of additional non-clinical and/or clinical studies and options related to marketing risk management plans. Additionally, FDA anticipates the public presentation of the recently reported study and other information at an advisory committee in the near future.
14. When was Trasylol approved?
Trasylol was approved in 1993.
15. Why was Trasylol approved?
Clinical studies showed that patients receiving Trasylol had less of a need for blood transfusions and less bleeding than patients receiving a placebo. These clinical studies did not detect an increase in the risk for serious side effects.
16. I've received Trasylol. Am I going to have some of these serious reactions?
In general, the serious side effects described in The New England Journal of Medicine report are the type of reactions that occur within days following CABG. Patients are unlikely to experience these side-effects from Trasylol after this time period.
17. Where can I find more information about Trasylol?
The package insert provides more information about Trasylol.