FDA Highlights Risk of Gadolinium Contrast Agents

BY ELIZABETH MECHCATIE

The Food and Drug Administration has requested a boxed warning explaining the increased risk of nephrogenic systemic fibrosis in patients with renal insufficiency be added to the labels of gadolinium-based contrast agents.

The FDA has requested that manufacturers add this information to the warnings section of the five marketed gadolinium-based contrast agents (GBCA), which are used to enhance the quality of magnetic resonance imaging.

The risk of nephrogenic systemic fibrosis (NSF) has been associated with exposure to GBCAs in patients with acute or chronic severe renal insufficiency (glomerular filtration rate less than 30 mL/min per 1.73 square meters) and in patients with acute renal insufficiency of any severity due to the hepatorenal syndrome or in the perioperative liver transplantation period.

"Health care professionals should avoid the use of a GBCA in these patients unless the diagnostic information is essential and not available with noncontrast enhanced magnetic resonance imaging," according to the FDA. No cases of NSF have been reported in patients with normal kidney function, or in mild to moderate kidney insufficiency.

The agency is advising that patients be screened for kidney problems before receiving a GBCA, and that the recommended dose not be exceeded and "enough time should elapse to ensure that a dose has been eliminated from the body before the agent is used again." Physicians should consider having hemodialysis patients undergo the procedure promptly after a GBCA is administered, according to the FDA, although it is not known whether hemodialysis prevents NSF.

NSF has been reported only in patients with acute or chronic severe renal insufficiency. Signs and symptoms include burning, itching, and reddened or darkened patches on the skin; yellow, raised spots on the whites of the eyes; joint stiffness and pain deep in the hip; and limited range of motion in the arms, legs, hands, or feet. The cause is not known, and there are no consistently effective treatments, according to the FDA.

Whether the risk of NSF is similar for all the agents is not known. GBCAs are also used off label for magnetic resonance angiography (MRA).

When asked to comment on this story, Dr. Vivian Gahtan, of SUNY Upstate Medical University and the Department of Veterans Affairs VA Healthcare Network Upstate New York at Syracuse, stated: "For diagnostic imaging, the trend has been to move away from conventional angiography to MRA or CT-angiography. NSF is associated with the use of gadolinium-based agents in patients with significant renal insufficiency.

"This recently identified association reinforces that there is risk [with] all contrast agents currently in use. In fact, the risks are better understood and treatment better defined with standard contrast agents used for CTA and conventional angiography. However, depending on the study needed using CTA, a significant volume of contrast may be required. At this juncture, the lowest risk related to contrast may be to perform catheter directed angiography in certain patients with renal dysfunction."