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

MRI Exablate neuro helmet from INSIGHTEC

MRI Exablate neuro helmet from INSIGHTEC. Image courtesy of Ali Rezai, M.D., and RSNA.

News | Clinical Trials | December 03, 2019
December 3, 2019 — Focused ultrasound is a safe and effective way to target and open areas of the blood-brain barrier
Reduction in fractional anisotropy (FA) in obese patients compared to the control group

Reduction in fractional anisotropy (FA) in obese patients compared to the control group: At the intersection of the alignment vectors, a large cluster of FA decrease located in the corpus callosum on the left. In red: Reduction of FA in obese patients compared to controls, and FA skeleton (green), superimposed on the mean of FA images in sample. Image courtesy of Pamela Bertolazzi, Ph.D., and RSNA.

News | Clinical Trials | November 25, 2019
November 25, 2019 — Researchers using magn...
Image by Volker Pietzonka from Pixabay

Image by Volker Pietzonka from Pixabay

News | Pediatric Imaging | November 25, 2019
November 25, 2019 — Connectivity in an area of the brain that regulates emotion may be altered in infants exposed to
Embrace Neonatal MRI is a U.S. Food and Drug Administration (FDA) cleared and CE marked compact magnetic resononance imaging (MRI) system ergonomically designed to fit inside the neonatal intensive care unit (NICU)
News | Magnetic Resonance Imaging (MRI) | November 25, 2019
November 25, 2019 — Embrace Neonatal MRI is a U.S.
FerrAlert technology automatically detects and logs ferromagnetic events and exclusively provides a photographic stream which is date and time stamped
News | Magnetic Resonance Imaging (MRI) | November 22, 2019
November 22, 2019 — Kopp Development Inc. acquired Mednovus, Inc.
The study finds it's possible to use commercial facial recognition software to identify people from brain MRI that includes imagery of the face
News | Magnetic Resonance Imaging (MRI) | November 15, 2019
November 15, 2019 — Though identifying data typically are removed from medical image files before they are shared for

Guerbet presented its Contrast&Care injection management solution at ECR 2018

News | Contrast Media | November 13, 2019
November 13, 2019 – Guerbet, a global specialist in...
An image on Brigham and Women's Hospital's 7T MRI system

An image on Brigham and Women's Hospital's 7T MRI system. Image courtesy of Brigham and Women's Hospital

News | Magnetic Resonance Imaging (MRI) | November 13, 2019
November 13, 2019 — Increased immune system activity along the surface of the brain, or meningeal inflammation, may b
Radiographer Apollo Exconde with his Lego concept open MRI for patient education.

Radiographer Apollo Exconde with his Lego concept open MRI for patient education.

News | Patient Engagement | November 11, 2019
November 11, 2019 — Radiographer Apollo Exconde...