my personal edition > thrombosis > news


  E-Mail this DGNews to a colleague

DGNews

FDA: Increased Risk of Mortality Associated With Tinzaparin Not Limited to Patients Over 90 Years

ROCKVILLE, Md -- December 2, 2008 -- The US Food and Drug Administration (FDA) has received information about the Innohep in Renal Insufficiency Study (IRIS) that was stopped in February 2008 by the study's Data Safety Monitoring Committee because of an interim finding of an increase in all-cause mortality in patients who received Innohep.

The multicentre European study was designed to evaluate the safety of tinzaparin (Innohep) compared with unfractionated heparin (UFH) in treating deep vein thromboses (DVT) and/or pulmonary emboli (PE) in patients aged 70 years or older who had impaired renal function.

At the time the study was stopped, 350 patients had completed 90 days of follow-up. Of these, 23 of the 176 (13%) patients treated with tinzaparin and 9 of the 174 (5%) patients treated with UFH had died.

From the information currently available to the FDA, there is no clear pattern as to the causes of death. The causes of death do not appear to be related to either overdosing or underdosing with an anticoagulant.

The currently available data are not sufficient to rule out the possibility of another DVT or PE, or both, in patients who received tinzaparin. Although preliminary data do not appear to indicate a manufacturing problem with tinzaparin or the UFH used in the study, the FDA cannot categorically rule out this possibility until a thorough analysis of the detailed manufacturing data is completed.

Information on the patients enrolled in the study, on the heparin used to manufacture the tinzaparin used, and on the heparin used in the study is still being collected and analysed.

In July 2008, the company revised the labelling information to restrict the use of tinzaparin in patients aged 90 years and older. However, the FDA is concerned that the preliminary data from the IRIS study suggest that the increased risk of mortality is not limited only to patients in this age group. Therefore, the FDA has requested that the company revise the labelling to better describe the overall study results which suggest that, when compared to UFH, tinzaparin increases the risk of death for elderly patients (aged 70 years or older) with renal insufficiency.

Healthcare professionals should consider the use of alternative treatments to tinzaparin when treating elderly patients aged over 70 years with renal insufficiency and DVT, PE, or both. The FDA will consider additional regulatory actions as appropriate after they receive and thoroughly review all applicable data from the manufacturer of tinzaparin.

In the period from March 1, 2001, to February 28, 2007, roughly 32.1 million people in 60 countries were treated with tinzaparin. The FDA Adverse Event Reporting System was searched on October 15, 2008, and identified 383 adverse events reports of all types worldwide with 96 having death as an outcome. Overall, 60 of the 383 reports were from the United States, including 6 deaths (ages 60-75); there were no deaths reported for patients 90 or older. There did not appear to be an increase in the number of reported deaths from 2006 to the present.

The FDA anticipates submission of the final IRIS study report in January 2009 and plans to complete its review soon thereafter. The FDA will communicate its conclusions and any resulting recommendations to the public at that time.

The FDA urges both healthcare professionals and patients to report side effects from the use of Innohep (tinzaparin) to the FDA's MedWatch Adverse Event Reporting programme
· online at www.fda.gov/medwatch/report.htm;
· by returning the postage-paid FDA form 3500 available in PDF format at www.fda.gov/medwatch/getforms.htm to 5600 Fishers Lane, Rockville, MD 20852-9787;
· by faxing the form to 1-800-FDA-0178; or
· by phone at 1-800-332-1088

SOURCE: US Food and Drug Administration

E-Mail this DGNews to a colleague

To print, use this version