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Behind the news

14 October 2014

This TGA behind-the-news article was published on 14 October 2014. Behind-the-news articles are published in response to issues that are of interest to the community at a point in time, for example, subjects that have been in the media.

The TGA is aware of a recent media report about fatal adverse events associated with Trasylol.

Trasylol is a medicine containing the active ingredient aprotinin that was withdrawn from the market on 6 November 2007. It remains on the Australian Register of Therapeutic Goods (ARTG) but is not being supplied or marketed by the Australian sponsor.

The TGA has been notified of the use of an unapproved version of this medicine in recent years under the Special Access Scheme for use in 'Category A' patients i.e. a patient who is seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment. Such use is predicated on the medical practitioner having the informed consent of the patient or guardian of the patient. Some patients may have been given Trasylol obtained through this scheme from 2012 onwards.

Trasylol first became available in Australia in the 1960's, before the implementation of the Therapeutic Goods Act 1989 or the formation of the TGA. Trasylol was first entered onto the ARTG in 1992 for the treatment and prevention of haemorrhagic and traumatic shock and prevention of post-operative complications, such as delay in wound healing or haemorrhage (this indication was later removed). The Product Information (PI) for Trasylol at that time included precautions for hypersensitivity (allergic) reactions.

In 1996, Trasylol was approved for use to prevent blood loss and reduce the need for blood transfusion in adults undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery, especially where the risk of bleeding was high or where blood transfusion was unavailable or unacceptable (which remains its only indication). The PI was revised to include precautions relating to kidney failure, heart attack and death in some patients. Further information regarding these potential adverse events was added to the PI in January 2007 and May 2007.

Between February 2006 and November 2007, the TGA undertook a safety review of Trasylol, as well as ongoing reviews as more data became available. It sought advice from the Adverse Drug Reactions Advisory Committee (ADRAC) in March 2006, June 2006 and March 2007.

Trasylol was withdrawn from the market on 6 November 2007 after preliminary results from the Blood Conservation Using Antifibrinolytics: A Randomised Trial in High-Risk Cardiac Surgery (also known as the BART clinical trial) suggested an increased risk of death for patients receiving Trasylol compared to those receiving the alternative medications of aminocaproic acid or tranexamic acid for control of bleeding during heart surgery. The TGA published a statement regarding the withdrawal on 9 November 2007.

From December 2007 to June 2008 a Limited Access Program provided Trasylol for the use of some medical practitioners. The use was only for coronary artery bypass surgery when it was considered the benefits outweighed the risks. The medical practitioner using Trasylol was provided with information about the outcomes of the BART study. The medical practitioner was also required to provide information to patients specifically about Trasylol and obtain written consent from the patient for its use.

Following the withdrawal from the market in November 2007, the TGA continued to review the available information about Trasylol. It also sought advice from ADRAC in July 2008 about the interim findings of the BART study. Based on these interim findings ADRAC found there were concerns about the safety of Trasylol.

The TGA continued to monitor emerging information from international regulators that were reviewing the same information.

Available studies at the time had various limitations and were inconsistent in their findings. Additionally, the possible alternative medicines were either not marketed in Australia (aminocaproic acid) or were not approved for use in heart surgery (tranexamic acid). Tranexamic acid is now approved by the TGA for use in heart surgery.

The TGA is aware that after reviewing the currently available information the therapeutic goods regulators in Canada and Europe have allowed Trasylol back into the marketplace for use in cardiac bypass surgery.

If consumers are concerned that they may have received this medicine in the past, or if they have any other questions or concerns about this issue, they should talk to their health professional.

Adverse event reports

Over the past 30 years, the TGA received a total of 28 adverse events associated with Trasylol or for aprotinin-containing products for which no trade name was specified. These reports can be found in the Database of Adverse Event Notifications (DAEN) on the TGA website.

Of these reports, there were six cases where death was the reported outcome. For five of the six deaths, the reports indicated that the medicine had been used in heart surgery. In one of the cases resulting in death, the patient suffered a heart attack.

In two of the non-fatal cases, the patients who received the medicine experienced kidney failure.

It should be noted that reports received by the TGA and published in the DAEN contain suspected adverse events that reflect the observations of the individual reporter. Adverse events are suspected of being associated with a medicine, but this relationship is usually not certain – the symptom may be related to the underlying illness or to other factors. There might be no relationship between the adverse event and the medicine.

In the cases involving patients receiving Trasylol during heart surgery, a large number of other medicines were administered around the same time, which makes it difficult to determine the relationship between an individual medicine and the adverse event. Even in cases where Trasylol is identified as the sole suspected medicine in DAEN, it is unlikely that it was the only medicine the patient received.

Reporting problems

Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.

The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.