Europeans find more gadolinium-related adverse reactions

November 6, 2006

Problems with gadolinium-containing contrast agents administered to patients with renal impairment are more common than originally estimated. The lack of awareness among radiologists about the potential dangers for those at high risk is striking, according to researchers.

Problems with gadolinium-containing contrast agents administered to patients with renal impairment are more common than originally estimated. The lack of awareness among radiologists about the potential dangers for those at high risk is striking, according to researchers.

In June 2006, the FDA advised against giving gadolinium-containing contrast agents during MRI exams to patients with renal impairment. The warning came after the Danish Medicines Agency reported that 25 patients with kidney failure developed a life-threatening condition known as nephrogenic systemic fibrosis (NSF, previously known as nephrogenic fibrosing dermopathy).

A survey conducted in August 2006 by the European Society of Urogenital Radiology, which has members in Europe and the U.S., revealed many more additional cases of NSF, according to Danish radiologist Dr. Henrik Thomsen, who collected the results. Thomsen now estimates the number of cases at around 250.

About three-quarters of these 250 cases originated in the U.S. In 90% of all cases from both sides of the Atlantic, patients had received gadodiamide (Omniscan, GE Healthcare). The type of agent used in the other 10% of cases is unknown.

Thomsen, a professor of radiology at the University of Copenhagen, stressed that his survey figures are preliminary and that the reports need to be confirmed with patient files.

Nonetheless, he told Diagnostic Imaging that gadodiamide should not be given to patients with end-stage renal failure, including those on dialysis.

"We have no evidence at this moment that the same should apply to other gadolinium-based contrast media. With other agents, the stability of the macrocyclic chelates is much better. Gadodiamide is the least stable of gadolinium-based agents," he said.

Five agents with gadolinium are approved for use in MR imaging in the U.S.: Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance. The FDA has not approved gadolinium contrast agents for MR angiography, which can require three times the dose of MRI.

The FDA said it is investigating all gadolinium-containing contrast agents to determine whether they do in fact cause the condition in patients with renal failure, as this patient group was not typically represented in premarketing studies. The agency advises prompt dialysis be performed in patients with advanced renal failure who receive a gadolinium-containing contrast agent.

Somewhat surprisingly, the European society survey showed that most respondents had never heard of NSF. In a recent editorial in European Radiology, Thomsen said it was striking that radiologists did not know of the condition, especially given the FDA's warning in June.

GE Healthcare, which sells gadodiamide, also issued a warning in June, but that missive had not been distributed in several countries. No other vendors have issued a warning as of early November, according to Thomsen.

GE said it sent a letter by direct mail to all customers in all markets where the health authorities permitted notification. Some authorities said they would prefer to have more information about the condition before they notified radiologists, according to a GE executive. The company also personally delivered letters to customers and posted a warning on its Web site.

No cases of NSF have been reported in patients with normal kidney function. Gadolinium contrast agents are widely used and have a high safety profile. Since the 1980s, 200 million patients have been given gadolinium contrast agents, and an estimated 30 million of these have received gadodiamide.

Still, the severe nature of the condition demands caution for those at high risk. NSF causes fibrosis of the skin and connective tissues throughout the body. Patients may lose mobility of joints, and the fibrosis could spread to other parts of the body. Treatment options are limited, and the condition can be fatal.

GE strongly urges caution in the administration of gadodiamide contrast in renally impaired patients. The mechanism of NSF/NFD is not currently well understood, and other issues (such as other drugs) may be contributing factors, the company said.

For more information, see the Diagnostic Imaging archives:

Gadolinium contrast may link to life-threatening condition

Contrast osmolality does not affect renal impairment

Expanding contrast options widen clinical utility of MRA

Dynamic contrast-enhanced MR imaging finally comes of age

Large Swedish study challenges safety of iso-osmolar agent

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