Gadolinium-based contrast agents (GBCAs) are approved by HSA for use in magnetic resonance imaging (MRI). Seven GBCAs registered in Singapore: gadodiamide (Omniscan®, GE Healthcare), gadopentetate dimeglumine (Magnevist®, Bayer Schering Pharma), gadoterate meglumine (Dotarem®, Guerbet), gadobutrol (Gadovist®, Bayer Schering Pharma), gadobenate dimeglumine (Multihance®, IDS Pharmaceutical Division), gadoversetamide (Optimark®, Tyco Healthcare) and gadoxetic acid (Primovist®, Bayer Schering Pharma).

HSA has been closely monitoring the association of NFD/NSF with these contrast agents since May 2006, following the first alert by GE Healthcare on NFD/NSF reported with the use of Omniscan® in patients with severe renal impairment. An article was published in July 2006 issue of the Adverse Drug Reaction News Bulletin to alert healthcare professionals on these adverse reactions.

Following the first alert on Omniscan®, more global reports of NFD/NSF were subsequently received for Omniscan® (more than 150 cases), as well as Magnevist® (78 cases) and Optimark® (11 cases). More recently, isolated cases associated with other GBCAs were also reported. All these reports occurred only in patients with renal dysfunction and is associated with swelling and tightening of the skin in the extremities which may develop over a period of days to several weeks. The mechanism by which a GBCA can cause NFD/NSF has not been elucidated but the current understanding is that GBCAs are associated with different levels of NFD/NSF risk based on their physicochemical and pharmacokinetic properties.

HSA has issued a Dear Healthcare Professional Letter (DHCPL) in December 2007 to all registered physicians to all physicians to alert them to the above safety information, as well as advise on appropriate use of these drugs. For details of the DHCPL, please log on to the MOH Health Professionals Portal at http://www.hpp.moh.gov.sg.

• Use of Omniscan® or Magnevist® is contraindicated in patients with severe renal failure (GFR < 30mL/min/1.72m2).
  
• The risk for the development of NFD/NSF in patients with moderate renal impairment is unknown, therefore Omniscan® and Magnevist® should be used with caution in patients with moderate renal impairment (GFR 30–59mL/min/1.73m2), especially if any gadolinium-based contrast media have been previously administered.
  
• Omniscan® and Magnevist® should be used in neonates and infants only if the benefits outweigh the risks as these patients have immature kidney functions.
  
• The other GBCAs should be used in patients with severe renal impairment (GFR < 30mL/min) only when absolutely necessary where the benefits outweigh their risks. Any possible alternative imaging tests that do not require GBCA, the clinical need for GBCA use, the relative risk for the patient, the type of agent to be used and any history of prior GBCA exposure should be considered when using the other GBCAs in severe renal impaired patients.
  
• There is no robust evidence to show that haemodialysis can prevent or treat the development of NFD/NSF, but haemodialysis shortly after GBCAs administration in patients currently receiving haemodialysis may be useful in removing the agent from the body, and there is some preliminary evidence that suggests NFD/NSF is less likely to develop in patients receiving early and adequate haemodialysis. If it is to be performed, the US and European authorities have recommended that at least two episodes of haemodialysis, the first commencing within 24 hours of administration of GBCA, should be performed in patients at risk who receive any of the GBCAs.