The European Medicines Agency (EMEA) has adopted a set of recommendations aimed at minimising the risk of nephrogenic systemic fibrosis (NSF) with gadolinium-containing contrast agents in patients at risk of developing the condition.
Gadolinium-containing contrast agents are used in patients undergoing magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA) scans. EMEA's Committee for Medicinal Products for Human Use (CHMP) reviewed these agents because of the association between the use of gadolinium-containing contrast agents and NSF, a rare, serious and sometimes life-threatening condition that is characterised by formation of connective tissues in the skin, joints, muscles and internal organs, in patients with severe kidney problems.
Because the risk of developing NSF depends on the type of gadolinium-containing contrast agent used, the active substances are classified into three categories of risk (high-, medium-, and low-risk groups). The CHMP's recommendations for the different agents vary according to their risk classification.
For high-risk gadolinium-containing contrast agents (Optimark®, Omniscan®, Magnevist®, Magnegita® and Gado-MRT ratiopharm®), the CHMP recommended contraindications in patients with severe kidney problems, in patients who are scheduled for or have recently received a liver transplant and in newborn babies up to four weeks of age. To minimise the risk of using these high-risk agents in patients with unknown kidney problems, the CHMP advised that all patients should be screened for kidney problems using laboratory tests before use. The CHMP also recommended that women should discontinue breastfeeding for at least 24 hours after a scan.
For medium- (Vasovist® ,Primovist® and MultiHance®) and low-risk agents (Dotarem®, ProHance® and Gadovist®), the CHMP recommended adding new warnings in the prescribing information concerning their use in patients with severe kidney problems and patients receiving a liver transplant. The CHMP recommended that all patients should be screened for kidney problems using laboratory tests before receiving these gadolinium-containing contrast agents and that the decision to continue or suspend breastfeeding for at least 24 hours after a scan should be taken by the doctor and the mother.
The CHMP recommended that the prescribing information of all gadolinium-containing contrast agents should include:
- a warning that the elderly may be at particular risk of NSF due to impaired ability of their kidneys to clear gadolinium from the body;
- a statement that there is no evidence to support the initiation of haemodialysis to prevent or treat NSF in patients not already undergoing haemodialysis
- a statement that the type and dose of contrast agent used should be recorded.
Based on currently available data, and with these risk minimisation measures in place, the CHMP considers that the balance of benefits and risks of these agents is acceptable.
Finally, the CHMP recommended that further studies should be carried out on the long-term retention of gadolinium in human tissues.
European Commission decisions on this opinion will be issued in due course
For further information, please contact Chief Medical Officer Doris I. Stenver, tel. +45 4488 9247 or +45 2246 0979.
Danish Medicines Agency, 20 November 2009