Article date: January 2010
The European Committee for Medicinal Products for Human Use (CHMP) has reviewed the risk of nephrogenic systemic fibrosis (NSF) with gadolinium-containing contrast agents.
On the basis of current evidence, the risk classification is as follows:
- High risk—Omniscan (gadodiamide), OptiMARK (gadoversetamide), Magnevist (gadopentetic acid)
- Medium risk—MultiHance (gadobenic acid), Primovist (gadoxetic acid), Vasovist (gadofosveset)
- Low risk—Gadovist (gadobutrol), ProHance (gadoteridol), Dotarem (gadoteric acid)
Nephrogenic systemic fibrosis
NSF, previously called nephrogenic fibrosing dermopathy (NFD), is a serious and life-threatening condition characterised by the formation of connective tissue in the skin which becomes thickened, coarse, and hard, sometimes leading to contractures and joint immobility. Patients with NSF can have systemic involvement of other organs including the lungs, liver, muscles, and heart.
Nine gadolinium-containing contrast agents are authorised in the EU to aid MRI of the body and of the blood vessels (magnetic resonance angiography, MRA)—see above.
The risk of NSF with these agents has been kept under close review since the association was first observed in January 2006.1 In August 2007, Drug Safety Update advised healthcare professionals that the risk of NSF was highest with Omniscan and OptiMARK, and that there was also evidence to suggest that Magnevist should not be used in patients at greater risk (ie, those with severe renal dysfunction).
In the recent review, CHMP has considered: the risk of NSF in patients with renal impairment; risk in patients in the perioperative liver-transplantation period; use in infants, neonates, and the elderly; use during pregnancy and lactation; the need for screening of renal function before use and dose restrictions; measures to accurately record the agent used; and what further studies are required.
Advice for healthcare professionals
The following risk-minimisation measures should be used for gadolinium-containing contrast agents for:
renal-function monitoring - this should be tested in all patients receiving high-risk agents, and is generally advisable for patients receiving medium-risk or low-risk agents. It is particularly important to screen patients aged 65 years or older
renal impairment - for patients with severe renal impairment (glomerular filtration rate [GFR] <30 mL/min/1·73m2), use of a high-risk agent is contraindicated. If use of a medium-risk agent cannot be avoided or if it is necessary to use a low-risk agent, a single lowest dose possible can be used and should not be repeated for at least 7 days. For patients with moderate renal impairment (GFR 30–59 mL/min/1·73 m2), if it is necessary to use a high-risk agent a single lowest dose possible can be used and should not be repeated for at least 7 days
perioperative liver-transplantation period - use of a high-risk agent is contraindicated. If use of a medium-risk agent cannot be avoided or if it is necessary to use a low-risk agent, a single lowest dose possible can be used and should not be repeated for at least 7 days
neonates - use of a high-risk agent is contraindicated. For medium-risk or low-risk agents, use a single lowest possible dose and do not repeat for at least 7 days
infants - use a single lowest dose of agent possible and do not repeat for at least 7 days
breastfeeding - discontinue for at least 24 hours after use of a high-risk agent. The decision of whether to continue or suspend breastfeeding for 24 hours after use of a medium-risk or low-risk agent should be at your discretion in consultation with the mother
pregnancy - use of any gadolinium-containing contrast agent is not recommended unless absolutely necessary
haemodialysis - there is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis
recording of the agent used - when they become available, peel-off tracking labels found on the vials, syringes, or bottles should be stuck onto the patient record to accurately record the name of the gadolinium contrast agent used. The dose used should also be recorded
reporting of suspected adverse reactions - on a Yellow Card for any suspected adverse reactions, including NSF, to gadolinium-containing contrast agents
Article citation: Drug Safety Update Jan 2010, vol 3 issue 6: 3.
Grobner T. Nephrol Dial Transplant 2006; 21: 1104–08. ↩