Local, State, Federal

FDA Revises GBCA Warning and Advises More NSF Screening

The US Food and Drug Administration (FDA) has issued a directive that will revise the existing boxed warning and other safety information within the labeling for gadolinium-based contrast agents (GBCAs), which are used extensively in MR imaging. The new warnings are intended to help prevent nephrogenic systemic fibrosis (NSF) occurring among patients who have, or may unknowingly have, dysfunctional kidneys or known kidney disease.

The FDA first issued an official Public Health Advisory about the risk of NSF in association with GBCAs in 2006. After further study, a boxed warning—the FDA’s strongest type of warning—was placed on GBCA labels in 2007 to tell clinicians and technologists to be cautious when giving GBCAs to patients with severe kidney dysfunction or kidney dysfunction of any severity if the patients also had certain types of liver problems.

Although the wording of the latest warning has not been set as of this writing, the FDA’s researchers have found sufficient data to specifically require three brands—Magnevist from Bayer Healthcare, Omniscan by GE Healthcare, and Optimark from Covidien—to be labeled “inappropriate for use among patients with acute kidney injury or chronic severe kidney disease.”

In addition, new warnings will apply to all GBCA brands, emphasizing the need to screen patients for NSF risks and detect unknown kidney dysfunction before administration.

In an e-mail interview with Axis Imaging News, Rafel (Dwaine) Rieves, MD, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, explained how the GBCA warning has changed.

Rieves wrote, “The new labeling better characterizes one of the high risk groups (‘acute kidney injury’), emphasizes the importance of screening patients, notes that some agents pose a higher risk than others for the most vulnerable patient population (see new contraindications [on the FDA Web site]); the text also emphasizes the need to actually record the agent (drug) administered to a patient and the dose; one of the particular concerns from post-marketing reports was the lack of information regarding which of the GBCAs was actually administered to a patient, as well as the dose.”

Rieves added that the studies the FDA used for its decision were based on evidence presented at the December 2009 advisory committee, which reviewed more than 1,200 reports of NSF associated with GBCAs.

As to why the label is being revised now and not in 2007 when the first black box warning was issued, Rieves responded, “By 2009, sufficient data (post-marketing reports, new animal and in vitro reports, published reports) had accumulated, such that a comprehensive reevaluation was regarded as appropriate. This review was presented at the December 2009 advisory committee; the ultimate labeling text was refined over the next several months and supplied to the manufacturers in early September 2010.”

As noted earlier, the specific label wording has not been approved as of this writing. However, the FDA’s September 10 press statement outlined the following core recommendations to health care professionals for all GBCAs:

  • Estimate kidney function through laboratory testing for patients at risk for chronically reduced kidney function;
  • Avoid use of GBCAs in patients suspected or known to have impaired drug elimination unless the imaging is essential and not available without contrast;
  • Monitor for signs and symptoms of NSF if a GBCA is administered to a patient with acute kidney injury or chronic, severe kidney disease;
  • Administer a GBCA only once during an imaging session.

For more specific information, physicians should refer to the online FDA Gadolinium Safety Announcement at www.fda.gov/Drugs/DrugSafety/ucm223966.htm.

—Tor Valenza