European authorities warn against use of Omniscan in at-risk patients

February 13, 2007

The European Medicines Agency has warned providers not to use gadodiamide (Omniscan) in patients with poor renal function, due to the risk of nephrogenic systemic fibrosis, a rare and life-threatening skin disease.

The European Medicines Agency has warned providers not to use gadodiamide (Omniscan) in patients with poor renal function, due to the risk of nephrogenic systemic fibrosis, a rare and life-threatening skin disease.

A 49 year-old man with terminal renal failure (GFR 10 mL/min) was first exposed to gadodiamide (0.3 mmol/kg) during an MRA study in April 2003. He developed progressive NSF with severe skin changes and cachexia. He had additional gadodiamide-enhanced scans after April 2003, resulting in a lifetime cumulative dose of 0.6 mmol/kg. He died 30 months after his first exposure. (Image courtesy of Dr. Peter Marckmann, department of nephrology at Copenhagen University Hospital in Herlev, Denmark)

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, may occur in patients with moderate to end-stage kidney disease after an MRI or MR angiography study with gadolinium-based contrast media. NSF causes problems in the joints and in some cases quickly results in loss of mobility or death.

In a decision released Feb. 7, the EMEA, the regulatory equivalent of the FDA for pharmaceutical product oversight for the European Union, advised that the agent should not be used in the following cases:

  • patients with severe renal impairment (glomular filtration rate <30 mL/min)
  • patients who have had a liver transplant or are awaiting liver transplantation

The agency also advised caution regarding the use of gadodiamide in neonates and infants up to one year old. Caution was again advised for all gadolinium-based agents administered to patients with severe renal impairment.

Cases of NSF were first reported in Europe in early 2006. The EMEA now says there have been 200 cases 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. As of Dec. 21, 2006, the FDA had received 90 U.S. case reports of NSF in patients who were administered a gadolinium-based MR contrast medium.

Currently, there are five FDA-approved gadolinium-based contrast agents: Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. These agents are approved for use during an MR scan but not for use with MRA, despite widespread off-label use.

Most cases of NSF have been linked to Omniscan and OptiMARK, which is sold in the U.S. but not approved in Europe, according to the EMEA. Most U.S. cases reported to the FDA were linked to Omniscan administration, according to the FDA Web site. A few cases have been associated with Magnevist at high doses, the EMEA reported.

Unlike the European agency, the FDA has taken a broader stance on the issue, advising caution for all gadolinium agents in high-risk patients. Kuo questioned that position in his pending March editorial. He concluded that Omniscan should not be used in patients with any level of renal disease.

NSF is very rare, and most cases are related to the specific agent Omniscan. Issuing a warning for all agents could unnecessarily deprive millions of patients access to gadolinium contrast, according to Kuo.

For more information from the Diagnostic Imaging archives:

FDA renews warning on gadolinium in patients with weak kidneys

Gadolinium-related problems stem from one specific agent

Europeans find more gadolinium related adverse reactions