Gadolinium-Based Contrast Agents

Gadolinium-based contrast agents

A CAR statement on its use and what you need to know

On March 10, 2017 the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended the suspension of the marketing authorizations of four linear gadolinium-based contrast agents (GBCAs) (Gadobenate dimeglumine [MultiHance], Gadopentetate dimeglumine [Magnevist], Gadodiamide [Omniscan], and Gadoversetamide [OptiMARK]) because of evidence that small amounts of gadolinium complexes may be retained in brain tissues after their intravenous use which is reported to occur with linear GBCAs. The PRAC did not recommend the suspension of the marketing authorization of another linear GBCA (Gadoxetate Disodium [marketed [Primovist®]) due to a cited lower administered dose and necessity for specific indications in liver MRI. The PRAC took this precautionary approach in the absence of known symptoms or diseases linked to gadolinium complexes in the brain.

It is important to note that this recommendation is not the final decision of the European Authorities on the benefit-risk balance of the GBCAs available in the European Union (EU), which will be taken at the end of a regulatory procedure called Referral, governed by article 31 of Directive 2001/83/EC. This will involve the completion of additional assessments to arrive at the final decisions on the various GBCAs.

The American College of Radiology (ACR) and the American Society of Neuroradiology (ASNR) issued a position statement in May 2016 on the use of GBCAs. It concurs that “residual gadolinium has been found within the brain tissue of patients who received multiple doses of GBCAs over their lifetimes. For reasons that remain unclear, gadolinium deposition appears to occur preferentially in certain specific areas of the brain, even in the absence of clinically evident disease and in the setting of an intact blood brain barrier. These findings led the FDA to publish a safety alert in July of 2015 indicating that they were actively investigating the risk and clinical significance of these gadolinium deposits. To date, no adverse health effects have been uncovered. A similar safety alert was published by Health Canada in January 2017.

When used appropriately, GBCAs provide essential information that helps physicians with the diagnosis and management of their patients. It is also noteworthy that GBCAs have overall a long and established track record of safety. Nonetheless, each time a gadolinium-enhanced MRI study is considered, it would be prudent to consider the clinical benefit of the diagnostic information provided by the study against the unknown potential risk of gadolinium deposition in the brain for each individual patient.

CAR addressing the issue

 In anticipation of the need for additional guidance for health care professionals and institutions, the CAR recently initiated the formation of a multidisciplinary guideline working group co-chaired by Drs. Reza Forghani and Nicola Scheida, both radiologists, for the evaluation of the current state of evidence on GBCA brain deposition and other general considerations pertaining to selection of a GBCA. The purpose of this committee is to review the current evidence, evaluate controversies, and provide guidance to health professionals on this important topic. This is in addition to the CAR’s multidisciplinary guideline working group co-chaired by Dr. Nicola Schieda, radiologist, and Dr. Swapnil Hiremath, nephrologist, that is currently in the process of updating recommendations for the use of GBCAs in renal impairment.

The CAR will remain vigilant and responsive to all available evidence on gadolinium retention. It will continue to monitor the safety of GBCAs and modify clinical practice guidelines recommendations accordingly as new data becomes available. Meanwhile health care professionals and institutions are encouraged to familiarize themselves with the current issues and controversies pertaining to the use of GBCAs, evaluate their practice patterns, and be vigilant in following the emerging literature and society guidelines on the use of these agents to ensure optimal practice. The CAR is dedicated to maintaining the highest standards of care, promoting patient safety and helping radiologists contribute to the very best health care for patients.

 

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