4 MRI Agents to Carry Warnings, 3 Agents Contraindicated for Patients With Kidney Disease

Disclosures

September 09, 2010

September 9, 2010 — Four gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) will feature a new label warning about the risk for nephrogenic systemic fibrosis (NSF) in certain patients with kidney disease, the US Food and Drug Administration (FDA) announced today. NSF is rare but potentially fatal.

Three GBCAs — gadopentetate dimeglumine (Magnevist; Bayer Healthcare Pharmaceuticals), gadodiamide (Omniscan; GE Healthcare), and gadoversetamide (Optimark; Mallinckrodt) — are now contraindicated for patients with acute kidney injury (AKI) or chronic severe kidney disease, as the risk for NSF is higher in this subgroup.

The 4 GBCAs that are approved for MRIs and that now will carry the new labeling are

  • gadofosveset trisodium (Ablavar; Lantheus Medical Imaging),

  • gadoxetate disodium (Eovist; Bayer Healthcare Pharmaceuticals),

  • gadobenate dimeglumine (Multihance; Bracco Diagnostics), and

  • gadoteridol (Prohance; Bracco Diagnostics).

The new warning label also applies to magnetic resonance angiography (MRA), which is used to detect heart problems, stroke, and vascular disease. Although the FDA has approved 7 GBCAs for MRI to sharpen images of body organs and tissues, only 1 agent — gadofosveset trisodium (Ablavar; Lantheus; previously known as Vasovist) — has been approved specifically for MRA. The FDA notes that both procedures can be performed without a contrast agent.

On the labels of all GBCAs, clinicians are advised to screen patients for AKI or chronic, severe kidney diseases before administering the agent and to monitor renal function after the patients receive a GBCA.

NSF is similar to scleroderma, in that excessive fibrous connective tissue forms in the skin, joints, eyes, and internal organs. Symptoms include scaling, hardening, and tightening of skin; red or dark skin patches; and stiffness. NSF has only been reported in patients with severe kidney disease, the FDA noted in its release announcing the labeling change. There is no known treatment, but improved renal function appears to it slow disease down and may even gradually reverse it, according to the FDA.

Gadolinium Found in Skin of Patients With NSF

The label requirements announced today stem from an ongoing review of the safety of GBCAs and strengthen warnings that the FDA ordered in 2007 regarding GBCAs and NSF.

The FDA first alerted the public to a possible link between the fibrosing disorder and GBCAs in 2006. The next year, researchers reported finding gadolinium in the skin of patients with NSF.

"Whether the GBCAs are the only agents or conditions that may be associated with NSF in patients with renal disease is unknown," the agency stated today. However, all the evidence suggests that GBCAs play a role in the development of NSF in such patients "due to the hepato-renal syndrome, or in the perioperative liver transplantation period."

The FDA has approved 2 MRI contrast agents that do not contain gadolinium, but these agents are indicated only for evaluating liver lesions.

Caution Advised for GBCAs in Patients With Poor Liver or Kidney Function

In addition to screening patients for AKI and chronic, severe kidney diseases, the FDA stated, clinicians considering the use of GBCAs in an MRI or MRA should

  • evaluate current kidney function through laboratory testing for patients at risk, including individuals older than 60 years and those with diabetes or hypertension;

  • avoid GBCAs with patients with or suspected of having impaired drug clearance, unless imaging is essential and is not possible without a contrast agent;

  • monitor for NSF signs and symptoms once GBCA is given to someone with AKI or chronic, severe kidney disease;

  • administer GBCA only once during an imaging session; and

  • instruct patients with kidney disease to contact a healthcare professional if they experience NSF signs and symptoms.

The FDA has asked manufacturers to continue to collect data on patients with renal insufficiency who have been given a GBCA. The agency will continue to evaluate new reports of NSF and may request more studies or label changes.

More information about today's announcement is available on the FDA's Web site.

To report adverse events related to GBCAs, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to MedWatch, FDA, 5600 Fishers Lane, Rockville, Maryland 20852-9787.

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