News | Contrast Media | August 29, 2017

European Medicines Agency Issues Update on Gadolinium Contrast Agents

European regulatory agency recommends suspension of marketing authorizations for some linear agents, restricted use of others; final opinion supports continued use of macrocyclic agents

European Medicines Agency Issues Update on Gadolinium Contrast Agents

August 29, 2017 — The European Medicines Agency (EMA) issued a final opinion that recommended restricting the use of some linear gadolinium-based contrast agents (GBCAs) and suspending the marketing authorizations of others, while supporting the continued use of macrocyclic GBCAs.

Importantly, the EMA confirmed that “there is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions for some intravenous linear agents in order to prevent any risk that could potentially be associated with gadolinium brain deposition.”

These recommendations are the second step in the European review process which is expected to be concluded with a final European Commission (EC) decision as early as September 2017.

There are no changes to the U.S. Food and Drug Administration (FDA) approval of GBCAs.

The recommendation of the EMA’s Committee for Medicinal Products for Human Use (CHMP) in their final opinion include:

  • Suspend the marketing authorizations of multipurpose linear GBCAs:
    • Magnevist i.v. (Active substance: gadopentetate dimeglumine; company: Bayer)
    • Omniscan (Active substance: gadodiamide; company: GE Healthcare)
    • OptiMark (Active substance: gadoversetamide; company: Guerbet)

Based on a review of the PRAC’s recommendation, the CHMP found that the benefit-risk balance is no longer favorable for certain linear GBCAs.

  • Confirms that macrocyclic GBCAs “…can continue to be used in their current indications but in the lowest doses that enhance images sufficiently and only when unenhanced scans are not suitable”:

Macrocyclic GBCAs

  • Gadovist (marketed as Gadavist in the U.S.)

Active substance: gadobutrol
Company: Bayer

  • ProHance

Active substance: gadoteridol
Company: Bracco

  • Dotarem

Active substance: gadoterate meglumine
Company: Guerbet

The CHMP outlined that “…macrocyclic agents are more stable and have a lower propensity to release gadolinium than linear agents.”

 

  • Recognizes that certain linear GBCAs are specifically indicated for continued use in liver imaging:

Liver imaging GBCAs

  • Primovist 0.25mmol/mL (liver-specific)

(Marketed as Eovist in the U.S.)
Active substance: gadoxetate disodium
Company: Bayer

  • MultiHance 0.5 mmol/mL

Active substance: gadobenate dimeglumine
Company: Bracco

View a comparison chart of MRI contrast agents. This will require a login, but it is free and only takes a minute to complete. 

 

The CHMP stated that Primovist (marketed as Eovist in the U.S.) and additionally MultiHance “can continue to be used for liver scans because they are taken up in the liver and meet an important diagnostic need.” The continued use of MultiHance represents a restriction of the product’s currently approved use to liver imaging only. MultiHance is not FDA-approved for liver imaging in the United States.

The opinion of the EMA’s CHMP affirms the recommendations of the PRAC following an assessment of literature published since 2014, regarding the presence of gadolinium in the brain and other tissues as well as information from manufacturers and experts in the field. While research has provided some insights, many questions remain, including whether there are any clinical implications.

In a May 22, 2017 update to its previous Drug Safety Communication, the FDA stated that “it has not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI).” The FDA further stated that it found “no evidence to date that gadolinium retention in the brain from any of the GBCAs, including those associated with higher retention of gadolinium, is harmful, restricting use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future.”

Further, the FDA stated, “Our recommendations for healthcare professionals and patients remain unchanged from July 2015 when we informed the public that we were investigating this potential risk with GBCAs. As is appropriate when considering the use of any medical imaging agent, healthcare professionals should limit GBCA use to circumstances in which additional information provided by the contrast agent is necessary, and assess the necessity of repetitive MRIs with GBCAs.” The FDA urges patients and healthcare professionals to report side effects involving GBCAs to the FDA MedWatch program.

The FDA evaluated scientific publications as well as adverse events reported to the agency and concluded that, "…To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis (NSF) that occurs in a small subgroup of patients with pre-existing kidney failure. NSF is a painful skin disease characterized by thickening of the skin, which can involve the joints and cause significant limitation of motion within weeks to months. Recent publications report cases of reactions involving thickening and hardening of the skin and other tissues in patients with normal kidney function who received GBCAs and did not have NSF; some of these patients also had evidence of gadolinium retention. We are continuing to evaluate such reports to determine if these fibrotic reactions are an adverse health effect of retained gadolinium..."

Read the article "Recent Trends and Developments in Contrast Media."

For more information: www.ema.europa.eu

Related Content

 Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Investigators led by a team at Massachusetts General Hospital (MGH) now describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated functionally intact brain connections and weeks later he recovered the ability to follow commands

Getty Images

News | Coronavirus (COVID-19) | July 08, 2020
July 8, 2020 — Many patients with severe coronavirus disease 2019 (...
A patient implanted with the Axonics System can undergo MRI examinations safely with radio frequency (RF) Transmit Body or Head Coil under the conditions outlined in the Axonics MRI Conditional Guidelines.

A patient implanted with the Axonics System can undergo MRI examinations safely with radio frequency (RF) Transmit Body or Head Coil under the conditions outlined in the Axonics MRI Conditional Guidelines.

News | Magnetic Resonance Imaging (MRI) | July 02, 2020
July 2, 2020 — Axonics Modulation Technologies, Inc., a medical technology company that has developed and is commerci
This data represents wave 2 of a QuickPoLL survey conducted in partnership with an imagePRO panel created by The MarkeTech Group (TMTG), regarding the effects of COVID-19 on their business

Getty Images

Feature | Coronavirus (COVID-19) | July 01, 2020 | By Melinda Taschetta-Millane
Researchers reviewed results of prostate biopsies on over 3,400 men who had targets identified on prostate MRI and found that the positive predictive value of the test for prostate cancer was highly variable at different sites
News | Prostate Cancer | July 01, 2020
July 1, 2020 — Prostate MRI is an emerging technology used to identify and guide treatment for...
R2* maps of healthy control participants and participants with Alzheimer disease. R2* maps are windowed between 10 and 50 sec21. Differences in iron concentration in basal ganglia are too small to allow visual separation between patients with Alzheimer disease and control participants, and iron levels strongly depend on anatomic structure and subject age. Image courtesy of Radiological Society of North America

R2* maps of healthy control participants and participants with Alzheimer disease. R2* maps are windowed between 10 and 50 sec21. Differences in iron concentration in basal ganglia are too small to allow visual separation between patients with Alzheimer disease and control participants, and iron levels strongly depend on anatomic structure and subject age. Image courtesy of Radiological Society of North America

News | Magnetic Resonance Imaging (MRI) | July 01, 2020
July 1, 2020 — Researchers using magnetic...
In new QuickPoLL survey on imaging during the pandemic, responses were tallied from around 170 radiology administrators and business managers, who are part of an imagePRO panel created by The MarkeTech Group (TMTG), regarding the effects of COVID-19 on their business. TMTG is a research firm specializing in the medical device, healthcare and pharmaceutical industries.
Feature | Coronavirus (COVID-19) | June 30, 2020 | By Melinda Taschetta-Millane
Cardiac MR can offer data above and beyond anatomical imaging, which is the main reason why this system was installed at Baylor Scott White Heart Hospital in Dallas. The system is a dedicated heart MRI scanner.

Cardiac MR can offer data above and beyond anatomical imaging, which is the main reason why this system was installed at Baylor Scott White Heart Hospital in Dallas. The system is a dedicated heart MRI scanner.

News | Pediatric Imaging | June 29, 2020
June 29, 2020 — A type of smart magnetic r...
This image of DCE-MRI reveals persistent blood brain barrier disorder in American football players. Using brain imaging techniques and analytical methods, researchers can determine whether football players have CTE by measuring leakage of the blood-brain barrier. Image courtesy of Ben-Gurion University

This image of DCE-MRI reveals persistent blood brain barrier disorder in American football players. Using brain imaging techniques and analytical methods, researchers can determine whether football players have CTE by measuring leakage of the blood-brain barrier. Image courtesy of Ben-Gurion University

News | Magnetic Resonance Imaging (MRI) | June 22, 2020
June 22, 2020 — Chronic traumatic encephalopathy (CTE), a neurodegenerative disease caused by repeated...