Caution Regarding Gadolinium Use is Appropriate, but Overreacting Can be Harmful
Wednesday, March 22, 2017
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA), which regulates pharmaceuticals in the EU, has recommended (link) “the suspension of the marketing authorizations for four linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.”
The agents are Gadobenic acid (MultiHance™, Bracco), Gadodiamide (Omniscan™, GE Healthcare), Gadopentetic acid, Magnevist™, Bayer HealthCare Pharmaceuticals), and Gadoversetamide (Optimark™, Guerbet). The PRAC recommendation is not equivalent with pulling the four linear agents off the market, but may trigger such action in the EU or elsewhere.
According to the press release, the committee took this “precautionary approach” because of the small risk that gadolinium deposits may cause long-term effects, although the group clearly stated that currently no symptoms or diseases have been linked to gadolinium in the brain. In contrast to macrocyclic agents, linear gadolinium compounds are more likely to leak free gadolinium, which raises the concern for potential tissue damage.
In Cardiovascular MR (CMR) applications, contrast-enhanced protocols are used for visualizing myocardial fibrosis, inflammation, and infarction, for MR angiography, and for first-pass perfusion scans. The use of gadolinium allows for a precise, qualitative and quantitative assessment of tissue changes.
The SCMR agrees with caution regarding the use of gadolinium agents, which similar to many other agents may have undesirable effects on the body, be it acute or chronic. As recommended by the PRAC, macrocyclic gadolinium compounds in the lowest reasonable dose should be used instead of linear agents whenever possible. The SCMR also strongly supports further research to better understand the potential impact of gadolinium deposits. On the other hand, it is important to consider that the diagnostic value of CMR scans can often be significantly increased by the use of contrast agents or even depends on them, with a clear benefit for therapeutic decision-making and eventually the patient. If a contrast-enhanced protocol provides significant diagnostic value, gadolinium should not be withheld because of concerns about potential tissue deposition. A phobia against all gadolinium agents or a move to other, less suitable imaging techniques would have far worse consequences for the patients.
It also must be emphasized that deposits have primarily been observed only after repeated or very high doses of contrast agent. Furthermore, the PRAC recommendation for suspension of marketing authorization does not apply to the macrocyclic agents Dotarem (Guerbet), Gadavist (Bayer HealthCare Pharmaceuticals), or Prohance (Bracco). The macrocyclic agents are more stable and have a lower propensity to release gadolinium and can be substituted for linear agents in any cardiovascular imaging application.