NSF deaths prompt GE to amend European label

February 16, 2007

GE Healthcare is struggling to understand the mechanism behind cases of nephrogenic systemic fibrosis, a rare and life-threatening skin disease associated with the death of some patients who have received GE’s MR contrast agent Omniscan (gadodiamide). The company is warning physicians against the use of this agent in patients with impaired kidney function, while working with the American College of Radiology and regulatory groups in Europe and the U.S.

GE Healthcare is struggling to understand the mechanism behind cases of nephrogenic systemic fibrosis, a rare and life-threatening skin disease associated with the death of some patients who have received GE's MR contrast agent Omniscan (gadodiamide). The company is warning physicians against the use of this agent in patients with impaired kidney function, while working with the American College of Radiology and regulatory groups in Europe and the U.S.

Last week, GE amended prescribing information in Europe regarding the agent to advise against its use in patients with severe renal impairment (glomular filtration rate <30 mL/min/1.73m²) and those who have had or are undergoing liver transplants. The company has not modified Omniscan labeling in the U.S., however, because the FDA process is different, according to GE spokesperson Kristin Silady.

"Our labeling information has to be in agreement with what the regulatory authorities in that jurisdiction feel is appropriate at that time," she said.

At least one other company has changed the labeling for its MR agent in Europe. Guerbet, which manufactures Dotarem, has added a caution regarding the use of this agent in patients suffering from chronic renal failure, even though no NSF cases have been linked to this product.

Regulatory authorities have received reports of NSF after the administration of other gadolinium-based contrast agents, but most of the current reports relate to Omniscan exposure. (GE estimates that 33 million doses have been administered since Omniscan was launched commercially in 1993.)

The European Medicines Agency has warned providers not to use Omniscan in patients with poor renal function. The FDA has gone further, advising caution in the use of all gadolinium agents in high-risk patients.

The FDA has approved five gadolinium-containing agents: Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. Although many cases of NSF have been linked to Omniscan, a few have also been associated with Magnevist and OptiMARK.

GE became aware of NSF cases tied to the administration of Omniscan in April 2006, according to Silady, and began issuing warnings to physicians in June. GE has now learned of 96 incidents of NSF occurring over the last several months after Omniscan administration, Silady. The European Medicines Agency estimates that 200 cases have occurred worldwide. In an article to appear in the March 2007 issue of Radiology, Dr. Phillip H. Kuo, an assistant clinical professor of radiology at Yale University, estimated the worldwide total at 400.

"We have put together a panel of experts in the field, trying to get people from all different sides of the issues together to figure out the problem," Silady said. "We are investigating it very heavily and trying to understand the mechanism."

Until more is known about the causal relationship between NSF and Omniscan, GE recommends alternative imaging modalities such as x-ray, when appropriate, for patients with compromised renal function. GE is also warning against the use of Omniscan in neonates younger than four weeks, noting it should be used in infants up to one year of age "only after careful consideration."

this story was updated Feb. 28, 2007