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Information for Healthcare Professionals: Gadolinium-Containing Contrast Agents for Magnetic Resonance Imaging (MRI) (marketed as Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance)

  

This information is not current.
The FDA has issued new information about this safety issue; please see Information on Gadolinium-Containing Contrast Agents.

FDA ALERT [06/2006]: Development of Serious and Sometimes Fatal Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy.

The FDA has learned of 25 foreign cases of Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD) in patients with renal failure who underwent Magnetic Resonance Angiography (MRA) with Omniscan. Omniscan and other gadolinium-containing contrast agents are FDA approved for use in Magnetic Resonance Imaging (MRI) but not for MRA. Physicians should carefully assess the need for performing MRI with contrast in patients with advanced renal failure (those currently requiring dialysis or with a Glomerular Filtration Rate (GFR)≤15cc/min) and administer the minimal needed dose of contrast agent if MRI with contrast is necessary. The FDA is further evaluating the possible link between the use of gadolinium-containing contrast agents and development of NSF/NFD.

This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about, this information. FDA intends to update this sheet when additional information or analyses become available.


To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program using the contact information at the bottom of this sheet.

Considerations

  • First identified in 1997, NSF/NFD is almost exclusively found in patients with renal failure and acidosis. Patients with this condition develop fibrosis of the skin and connective tissues throughout the body. The skin thickening may inhibit flexion and extension of joints, resulting in contractures. In addition, patients may develop widespread fibrosis in other organs. A skin biopsy is necessary to make a definitive diagnosis. The disease is progressive and may be fatal. Its cause is unknown.
  • Patients who receive gadolinium-containing contrast agents should be aware of the following possible signs and symptoms of NSF/NFD and advised to seek medical attention if these occur: swelling and tightening of the skin; difficulty extending the joints of arms, hands, legs, and feet; weakness, reddened or darkened areas on the skin; burning or itching of the skin; and deep bone pain in the hips and ribs.
  • Physicians should be cautious regarding the use of gadolinium-containing contrast imaging agents, especially at high doses, in patients with advanced renal failure (those currently requiring dialysis or with a GFR≤15cc/min).
  • There are no data to determine the utility of dialysis to prevent or treat NSF/NSD in patients with decreased renal function who receive gadolinium contrast MRA. However, prompt dialysis of these patients will eliminate circulating gadolinium, with average gadolinium excretory rates of 78%, 96%, and 99% in the first to third hemodialysis sessions, respectively.1

Data Summary

The Danish Health Authority (DHA) notified FDA of 25 reported cases of NSF/NFD from two European medical centers (one in Denmark, the other in Austria). All of these NSF/NFD cases occurred in patients with renal failure who underwent MRA with a single dose of Omniscan (which was the only gadolinium-containing contrast agent available in these two European medical centers). The patients developed NSF/NFD within 3 months (range 2 weeks to 3 months) after receiving Omniscan. The five patients from Austria are described in an April 2006 publication.2

Five gadolinium-containing contrast agents (Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance) are approved in the U.S. for magnetic resonance imaging (MRI). None are approved for MRA. The administered dose of gadolinium-containing contrast with MRA is often higher (up to three times) than the approved dose for MRI.

Worldwide, approximately 200 cases of NSF/NFD have been reported. Efforts are underway to determine how many of these patients received gadolinium-containing contrast agents. In addition, FDA is evaluating the 25 cases from the DHA, reports submitted to the FDA through the MedWatch program, and other studies in the literature. The FDA has also consulted with outside experts to further understand NSF/NFD. The FDA has contacted the manufacturers of the five U.S.-approved gadolinium-containing contrast agents and asked that they review their safety databases for cases of NSF/NFD and similar adverse events that occurred in patients who received gadolinium-containing contrast agents.

References

1 Okada S et al. Safety of gadolinium contrast agent in hemodialysis patients. Acta Radiologica 2001; 42: 339-341.

2 Grobner T. Gadolinium-a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis. Nephrology Dialysis Transplantation 2006; 21: 1104-1108.
 

Report serious adverse events toFDA’s MedWatch reporting system either online, by regular mail or by fax, using the contact information at the bottom of this page.

 

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