Gadolinium MRA Contrast Agent Approved by FDA with Warnings about Nephrogenic Systemic Fibrosis

The FDA has approved a new gadolinium-based contrast agent, Vasovist Injection, which is the first imaging agent approved for use during Magnetic Resonance Imaging (MRA) examinations.

Like other gadolinium contrasts that are approved for use during Magnetic Resonance Imaging (MRI) tests, the Vasovist injection will carry a “black box” warning about the potential risk of nephrogenic systemic fibrosis (NSF), a rare, but potentially fatal side effect.

An MRA is a test that provides detailed images of blood vessels. In particular, it is used to evaluate the blood vessels in the head, neck, lungs, kidneys and legs, to aid in detection of heart disorders, strokes and vascular diseases. Although a contrast agent is not required, the use of gadolinium contrast dye injected intravenously provides better images.

Prior to the approval of Vasovist, many radiologists injected one of the five other gadolinium contrast agents “off-label.” Although the contrast agents are only approved by the FDA for use during MRIs, doctors were free to administer them for “off-lable” during MRAs, which required substantially more of the contrast agents then what was typically used during an MRI.

Vasovist Injection (gadofosveset trisodium), which is manufactured by Epix Pharmaceuticals Inc., was approved by the FDA on December 24, 2008, as the first contrast agent specifically approved for use in MRA exams.

The primary safety risks associated with Vasovist are allergic reactions and nephrogenic systemic fibrosis (NSF), which is a rare disease which is only known to occur among individuals with moderate to severe kidney impairment who have been given a gadolinium contrast agent.

Nephrogenic systemic fibrosis, which is also commonly referred to as nephrogenic fibrosing dermopathy, involves a hardening and thickening of the skin and other internal organs. There is no known cure of the condition and in many cases it is leads to death.

In May 2007, the FDA required that a black box warning be added to gadolinium MRI contrast agents, which is the strongest warning that can be placed on a prescription medication. The warning recommends screening patients for renal insufficients and indicates that gadolinium dye should be avoided among those with kidney problems.

The manufacturers of gadolinium MRI contrast agents currently face around 400 NSF lawsuits filed by individuals who have developed the condition. The lawsuits allege that the manufacturers failed to adequately warn about the risk of this devastating condition.

All gadolinium lawsuits filed in federal court have been consolidated in an MDL, or multidistrict litigation, that has been centralized in the United States District Court for the Northern District of Ohio. The first cases are expected to go to trial towards the end of next year or early 2010.