NSF Uncommon After Contrast Agent Black Box Warnings

GAITHERSBURG, MD. — Black box warnings that have been added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none during the past year, according to an analysis by Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees.

Event dates are based on either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006, when 194 event dates were reported.

This reporting “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents. The warnings caution that patients with severe kidney insufficiency who receive gadolinium-based agents are at increased risk for the development of NSF.

In addition, patients who are in need of a liver transplantation, those who have just undergone liver transplantation, patients who have chronic liver disease, and patients experiencing kidney insufficiency of any severity also have an increased risk of NSF.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine); Omniscan (gadodiamide); OptiMARK (gadoversetamide); MultiHance (gadobenate dimeglumine); and ProHance (gadoteridol).

As of September 2009, a total of 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics). These numbers are based on reported cases in which a patient had known exposure to only one gadolinium-based contrast agent.

Although there was no formal vote during the committee meeting, the FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out contrast agents that increase the risk of NSF.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority of the committee members recommended that the use of Omniscan and OptiMARK be contraindicated in patients who have severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language. As for the other agents, “there was no clear evidence that any one single agent was safe in this patient population,” Dr. Harrington noted.

GAITHERSBURG, MD. — Black box warnings that have been added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none during the past year, according to an analysis by Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees.

Event dates are based on either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006, when 194 event dates were reported.

This reporting “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents. The warnings caution that patients with severe kidney insufficiency who receive gadolinium-based agents are at increased risk for the development of NSF.

In addition, patients who are in need of a liver transplantation, those who have just undergone liver transplantation, patients who have chronic liver disease, and patients experiencing kidney insufficiency of any severity also have an increased risk of NSF.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine); Omniscan (gadodiamide); OptiMARK (gadoversetamide); MultiHance (gadobenate dimeglumine); and ProHance (gadoteridol).

As of September 2009, a total of 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics). These numbers are based on reported cases in which a patient had known exposure to only one gadolinium-based contrast agent.

Although there was no formal vote during the committee meeting, the FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out contrast agents that increase the risk of NSF.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority of the committee members recommended that the use of Omniscan and OptiMARK be contraindicated in patients who have severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language. As for the other agents, “there was no clear evidence that any one single agent was safe in this patient population,” Dr. Harrington noted.

GAITHERSBURG, MD. — Black box warnings that have been added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none during the past year, according to an analysis by Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees.

Event dates are based on either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006, when 194 event dates were reported.

This reporting “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents. The warnings caution that patients with severe kidney insufficiency who receive gadolinium-based agents are at increased risk for the development of NSF.

In addition, patients who are in need of a liver transplantation, those who have just undergone liver transplantation, patients who have chronic liver disease, and patients experiencing kidney insufficiency of any severity also have an increased risk of NSF.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine); Omniscan (gadodiamide); OptiMARK (gadoversetamide); MultiHance (gadobenate dimeglumine); and ProHance (gadoteridol).

As of September 2009, a total of 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics). These numbers are based on reported cases in which a patient had known exposure to only one gadolinium-based contrast agent.

Although there was no formal vote during the committee meeting, the FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out contrast agents that increase the risk of NSF.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority of the committee members recommended that the use of Omniscan and OptiMARK be contraindicated in patients who have severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language. As for the other agents, “there was no clear evidence that any one single agent was safe in this patient population,” Dr. Harrington noted.