FDA suggests labeling change for low–molecular-weight heparin

The FDA announced yesterday that it has received information from the Innohep in Renal Insufficiency Study that was stopped in February. Based on this information, the FDA has suggested that the manufacturer revise the labeling to indicate a potential increased risk of death for patients aged 70 years and older with renal insufficiency.

The IRIS study’s Data Safety Monitoring Committee stopped the study in February after finding an increase in all-cause mortality for patients who received the low–molecular-weight heparin, tinzaparin (Innohep, Pharmion LLC). European researchers conducted the IRIS study to evaluate the safety of tinzaparin compared with unfractionated heparin to treat deep vein thrombosis or pulmonary embolism in patients aged older than 70 years who had impaired renal function, according to a press release.

Three hundred fifty patients had completed 90 days of follow-up when the study was stopped. Deaths included 23 of 176 patients (13%) who received tinzaparin and nine of 174 patients who received unfractionated heparin. In July, Pharmion revised the labeling to restrict the use of tinzaparin in patients aged 90 years and older, according to the press release. The FDA is now concerned that this risk is not limited only to patients in that age range and has requested that Pharmion revise the labeling again.

In the press release, the FDA wrote that the currently available information did not indicate a clear pattern in the causes of death, and the causes do not appear to be related to bleeding or blood clots from use of an anticoagulant. The FDA also said it is not possible to rule out another deep vein thrombosis or pulmonary embolism as the cause of death in patients who received tinzaparin or to rule out a manufacturing problem with the product, although the data does not indicate this possibility.

The FDA reported that a search of its Adverse Event Reporting System on Oct. 15, 2008 found 383 adverse events with tinzaparin, 96 of which resulted in death. Sixty of the 383 reports were from the United States and six of these were death; no deaths were reported for people aged 90 years and older.

The FDA and the company continue to collect and analyze data on the study patients. The FDA suggested that health care professionals consider using alternative treatments in this patient population. The agency also urged health care professionals and patients to report any side effects from use of tinzaparin to its MedWatch Adverse Event Reporting program.