Gadolinium-Containing Contrast Agents - Update on Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD) - Notice to Hospitals

Starting date:

November 14, 2013

Posting date:

November 14, 2013

Type of communication:

Notice to Hospitals

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-36711

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  Related AWRs

Notice about Health Canada advisories

NOTICE TO HOSPITALS - Health Canada Issued Important Safety Information on Gadolinium-Based Contrast Agents

November 14, 2013

To:    Hospital Chief of Medical Staff

Please distribute to Departments of Radiology, Nephrology, Emergency Medicine, Internal Medicine, Nursing, Intensive Care and other involved professional staff and post this NOTICE in your institution.

Subject:     Update on Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD) associated with the Use of Gadolinium-Containing Contrast Agents

Gadolinium (Gd)-containing contrast agents (GBCA) are indicated for providing contrast enhancement in the magnetic resonance imaging (MRI) investigations. Eight GBCA products are currently authorized for sale in Canada: Ablavar (gadofosveset trisodium) Gadovist (gadobutrol), Magnevist (gadopentetate dimeglumine), MultiHance (gadobenate dimeglumine), Omniscan (gadodiamide), OptiMARK (gadoversetamide), ProHance (gadoteridol) and Primovist (gadoxetate disodium).

These contrast agents have been linked to a rare and potentially fatal disease, Nephrogenic Systemic Fibrosis (NSF) in patients with kidney disease^{Footnote 1}. While NSF development is considered a potential class-related effect of all GBCAs, current evidence suggests that the extent of risk for NSF following exposure to any specific GBCA vary among the agents.  Health Canada has worked with the Canadian Marketing Authorization Holders of the GBCAs to update the prescribing information for these agents.

The current Canadian prescribing information for GBCAs is outlined in the box below.

• OMNISCAN, OPTIMARK and MAGNEVIST are contraindicated in:
  • Patients with chronic severe renal insufficiency where glomerular filtration rate is 2;30>
  • Patients with acute kidney injury (AKI) (including those with acute renal insufficiency of any severity due to the hepato-renal syndrome or patients in the perioperative liver transplantation period) and
  • Neonates up to 4 weeks of age due to their immature renal function.
• GADOVIST, ProHANCE, MultiHANCE, ABLAVAR and PRIMOVIST should only be used with extreme caution in patients mentioned above.
• All patients should be screened for AKI, renal dysfunction and reduced renal function prior to therapy.

NSF can result in fatal or debilitating systemic fibrosis. In such cases, the skin fibrosis extends beyond the dermis and involves subcutaneous tissues, muscles and internal organs^{Footnote 2},^{Footnote 3}. The disease was first described in the medical literature in 2000^{Footnote 2}. A skin biopsy is necessary to exclude skin disorders with similar presentation.

NSF cases have been reported following single and multiple administrations of GBCAs. It is not always possible to identify a single causal agent. NSF has also been reported to occur following the sequential administration of some lower risk GBCAs.

Repeated or higher than recommended doses of a GBCA and the degree of renal function impairment at the time of exposure are risk factors for NSF^{Footnote 4}. The risk of NSF in patients with mild to moderate renal insufficiency is not well characterized, and the cautious utilization of the lowest possible dose of GBCA in these patients is recommended. When administering a GBCA, the recommended dose should not be exceeded and a sufficient period of time should be allowed for elimination of the agent from the body prior to any re-administration.

For patients receiving hemodialysis, healthcare professionals may consider prompt hemodialysis following GBCA administration in order to enhance the contrast agent's elimination. However, it is not known currently if hemodialysis can help to prevent NSF.

Health Canada has previously issued a number of risk communications to inform Canadians about this safety concern. These could be found at the following links:

• January 12, 2010 - Healthcare Professional Communication and Public Communication - Association of OPTIMARK (gadoversetamide injection) with Nephrogenic Systemic Fibrosis (NSF)
• October  2007 Canadian Adverse Reaction Newsletter: Gadolinium-containing agents: update on nephrogenic systemic fibrosis
• March 13, 2007 - Notice to Hospitals - Association of gadolinium-containing contrast agents and Nephrogenic Systemic Fibrosis /Nephrogenic Fibrosing Dermopathy (NSF/NFD)
• March 13, 2007 - Health Canada advises Canadians of safety issues related to gadolinium-containing contrast agents used in magnetic resonance imaging (MRI)
• July 12, 2006- Healthcare Professional Communication - Association of Nephrogenic Systemic Fibrosis /Nephrogenic Fibrosing Dermopathy (NSF/NFD) with the use of gadolinium (Omniscan™).

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any cases of NSF or other serious or unexpected adverse reactions in patients receiving any of the brand names previously mentioned should be reported to Health Canada at the following address:

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345, or
   
• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Related AWRs

Updated Safety Information for Gadolinium-Based Contrast Agents

2013-11-14 | Health products

Advisory