News | Contrast Media | March 13, 2017

European Committee Releases New Recommendations on Gadolinium-based Contrast Agents

Committee recommends suspension of marketing authorization for four linear gadolinium contrast agents that are more likely to leave deposits in the brain following MRI exams

PRAC, European Medicines Agency, gadolinium-based contrast agents, safety recommendations, brain MRI

March 13, 2017 — The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency recently released new recommendations on procedures employing gadolinium-based contrast agents, in which the committee recommended suspension of marketing authorization for four agents.

The EMA initiated a review last March of the risk of gadolinium deposition in brain tissue following the repeated use of gadolinium contrast agents in patients undergoing magnetic resonance imaging (MRI) scans.1 After carrying out an almost year-long, in-depth review of the risk of brain deposits and of the overall safety of these products, the PRAC recommendations2 are as follows:

“EMA’s Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended 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 concerned are intravenous injections of gadobenic acid, gadodiamide, gadopentetic acid and gadoversetamide, which are given to patients to enhance images from magnetic resonance imaging (MRI) body scans. (...)

The four agents recommended for suspension are referred to as linear agents. Linear agents have a structure more likely to release gadolinium, which can build up in body tissues.

Other agents, known as macrocyclic agents, are more stable and have a much lower propensity to release gadolinium. The PRAC recommends that macrocyclic agents3 be used at the lowest dose that enhances images sufficiently to make diagnoses and only when unenhanced body scans are not suitable.

Some linear agents will remain available: gadoxetic acid, a linear agent used at a low dose for liver scans, can remain on the market as it meets an important diagnostic need in patients with few alternatives. In addition, a formulation of gadopentetic acid injected directly into joints is to remain available because its gadolinium concentration is very low – around 200 times lower than those of intravenous products. Both agents should be used at the lowest dose that enhances images sufficiently to make diagnoses and only if unenhanced scans are not suitable. (...)”

The recommendations also note that “the companies concerned by this review have the right to request the PRAC to re- examine its recommendations.

The PRAC’s final recommendations will be sent to the Committee for Medicinal Products for Human Use (CHMP) for its opinion. Further details will be published at the time of the CHMP opinion.”

Guerbet, which markets the macrocyclic gadolinium-based contrast agents Dotarem and Artirem, as well as Optimark, a product belonging to the class of linear gadolinium-based contrast agents, voiced its agreement with the PRAC recommendations and said it does not intend to request a re-examination. The company said it is strongly committed to providing healthcare professionals with a comprehensive range of effective and safe contrast media in order to improve diagnosis, prognosis and quality of life for patients.

Watch the video “MRI Gadolinium Contrast Retention in the Brain.”

Read the feature story “Gadolinium May Remain in Brain After Contrast MRI.”

For more information:


1. containing_contrast_agents/human_referral_prac_000056.jsp&mid=WC0b01ac05805c516f
2. Gadolinium Article-31 referral - PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension for some marketing authorisations. 10/03/2017

Related Content

Ligand Establishes Program to Develop Captisol-Enabled, Next-Generation Diagnostic Imaging Contrast Agents
News | Contrast Media | January 19, 2018
Ligand Pharmaceuticals Inc. announced initiation of a program to develop contrast agents with reduced renal toxicity....
FDA Holds MIDAC Meeting on Gadolinium-Based Contrast Agents. Image by Marilyn Fornell
News | Contrast Media | September 07, 2017
The U.S. Food and Drug Administration (FDA) announced it would hold a meeting of the Medical Imaging Drugs Advisory...
European Medicines Agency Issues Update on Gadolinium Contrast Agents
News | Contrast Media | August 29, 2017
August 29, 2017 — The European Medicines Agency (EMA) issued a final opinion that recommended restricting the use of
Guerbet Announces Plans to Streamline Contrast Media Portfolio, gadolinium MRI contrast
News | Contrast Media | July 18, 2017
Guerbet recently announced that it will phase out sales throughout the world of two products: Hexabrix (meglumine and...
ACR Offers Revised Contrast Media in Imaging Manual
News | Contrast Media | July 17, 2017
The American College of Radiology (ACR) recently revised its authoritative guide for the safe and effective use of...
Bayer Arterion contrast Injector used to administer medical imaging contrast for CT scans.

Bayer Healthcare's Arterion contrast injector system.

Feature | Contrast Media | June 19, 2017 | Dave Fornell
Here are several updates in medical imaging...
Lantheus Medical Imaging, Definity, FDA approval, label update, echocardiography, cardiac shunt contraindication
Technology | Contrast Media | February 02, 2017
Lantheus Medical Imaging Inc. announced U.S. Food and Drug Administration (FDA) approval of a label update for Definity...
CT, computed tomography, IV contrast media, acute kidney injury risk, Annals of Emergency Medicine study

A new study in Annals of Emergency Medicine finds no association between intravenous contrast media used in computed tomography (CT) and kidney damage. Roughly 80 million doses of IV contrast media are given every year. Credit: American College of Emergency Physicians

News | Contrast Media | January 30, 2017
Intravenous contrast media (typically iohexol or iodixanol) used in computed tomography (CT) does not appear to be...
GE Healthcare, Optison ultrasound contrast agent, FDA labeling change, cardiac shunts, intra-arterial injection
Technology | Contrast Media | October 04, 2016
GE Healthcare announced that the U.S. Food and Drug Administration (FDA) has approved a label change for the ultrasound...
MR angiography, MRA, Bayer, Gadavist, gadobutrol injection, FDA approval, supra-aortic arteries
Technology | Contrast Media | April 29, 2016
Bayer announced that the U.S. Food and Drug Administration (FDA) has approved Gadavist (gadobutrol) injection for use...
Overlay Init