The Food and Drug Administration has requested that 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, according to an alert posted on the agency's MedWatch Web site.
Joint pain is a common finding in patients who develop nephrogenic systemic fibrosis.
The FDA has requested that the manufacturers add this information to the warnings section of the prescribing information 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 these agents 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, according to the FDA.
“Healthcare 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 alert. No cases of NSF have been reported in patients with normal kidney function, or mild to moderate kidney insufficiency.
The agency is advising patients be screened for kidney problems before they receive one of the imaging agents, and the recommended dose should not be exceeded.
Physicians should consider having hemodialysis patients undergo the procedure promptly after a GBCA is administered, according to the FDA. Clearance rates of GBCA have been reported to be as high as 99% after three hemodialysis sessions, although it is not known whether hemodialysis prevents NSF.
NSF—a debilitating and potentially fatal disease identified in 1997, which affects the skin, muscle, and internal organs—has been reported only in patients with acute or chronic severe renal insufficiency. Signs and symptoms include joint stiffness and pain deep in the hip as well as limited range of motion in the arms, legs, hands, or feet.
Whether the risk of NSF is similar for all the agents is not known. Postmarketing reports show that Omniscan (manufactured by GE HealthCare) is the most commonly reported agent, followed by Magnevist (Bayer Schering Pharma) and OptiMark (Mallinckrodt).
GBCAs are used off label for magnetic resonance angiography (MRA), but “some radiologists believe that these agents help provide detailed images of blood vessels,” according to the FDA.
The FDA first notified health care professionals about this risk in June 2006, after learning about 25 such reports in Denmark, and updated the information on the risk in December 2006.
More information is available at www.fda.gov/medwatch/safety/2007/safety07.htm#Gadoliniumwww.fda.gov/medwatch