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

Two magnetic resonance imaging (MRI) findings — joint capsule edema and thickness at the axillary recess, specifically — proved useful in predicting stiff shoulder in patients with rotator cuff tears, according to an ahead-of-print article in the May issue of the American Journal of Roentgenology (AJR)

A: Oblique coronal fat-suppressed T2-weighted MR image shows normal hypointense joint capsule at axillary recess (arrow). Note full-thickness tear of supraspinatus tendon (arrowheads) B: Oblique sagittal proton density MR image shows preserved subcoracoid fat triangle (asterisk). Image courtesy of the American Journal of Roentgenology (AJR)

News | Magnetic Resonance Imaging (MRI) | February 20, 2020
February 20, 2020 — Two ma...
Hyperfine Research, Inc. announced that it has received U.S. Food and Drug Administration (FDA) 510(k) clearance for the world’s first bedside Magnetic Resonance Imaging (MRI) system

Hyperfine's point-of-care MRI wheels directly to the patient’s bedside, plugs into a standard electrical wall outlet, and is controlled via a wireless tablet. Photo courtesy of Business Wire

News | Magnetic Resonance Imaging (MRI) | February 12, 2020
February 12, 2020 — Hyperfine Research, Inc. announced that i
The magnetic resonance imaging (MRI) contrast agents market is expected to grow rapidly

Image courtesy of GE Healthcare

News | Magnetic Resonance Imaging (MRI) | February 11, 2020
February 11, 2020 — The magnetic resonance imaging (MRI) contrast agents market is expected to grow rapidly in the fo
Gadolinium-based contrast agents

UT Dallas faculty members who collaborated with Dr. Jeremiah Gassensmith (center, back), associate professor of chemistry and biochemistry, include Dr. Lloyd Lumata (left, back), assistant professor of physics, and Dr. Steven Nielsen, associate professor of chemistry. Chemistry graduate students in Gassensmith’s lab include (from left, front) Oliva Brohlin, Arezoo Shahrivarkevishahi and Laurel Hagge.

News | Contrast Media | February 06, 2020
February 6, 2020 — University of Texas at Dallas researchers
Qynapse, a medical technology company, announced that it received U.S. Food and Drug Administration (FDA) 510(k) clearance for its QyScore software
News | Information Technology | February 04, 2020
February 4, 2020 — Qynapse, a medical technology company, anno
RSNA 2019

RSNA 2019

Feature | Radiology Imaging | January 31, 2020 | By Greg Freiherr
The founder of Gonzo journalism thought
This image is of an 80 kg woman with a newly diagnosed IDH-wildtype glioblastoma

This image is of an 80 kg woman with a newly diagnosed IDH-wildtype glioblastoma. The quarter dose image on the left was obtained after the administration of 4 ml of MultiHance. Subsequently, an additional 12 ml of MultiHance was administered and the cumulative full dose image in the center was obtained. The image on the right was rendered following artificial intelligence processing of the 4 ml image using eGad genetic algorithms. This image has the quality of triple dose gadolinium even though only one quarter dose gadolinium was given.

Feature | Contrast Media Injectors | January 30, 2020 | By Matthew Kuhn, M.D., FACR
Gadolinium-based contrast agents (...
The researchers used high resolution cross-sectional imaging with CT or MRI to assess 225 men with abdominal aortic aneurysm. Follow-up lasted, on average, more than three years.  Slightly more than half of patients had an intraluminal thrombus. The aneurysms of those with intraluminal thrombus were larger at baseline and grew by a rate of 2 mm per year, twice as fast as the 1 mm per year growth rate in people without intraluminal thrombus.
News | Computed Tomography (CT) | January 29, 2020
January 29, 2020 – The presence of a blood clot on the wall of the aorta in people with...
Gadolinium based contrast dye in brain MRI

Gadolinium contrast agents (GBCAs) are partly retained in the brain, raising safety concerns, as seen in this MRI.

News | Contrast Media | January 17, 2020
January 17, 2020 — Bracco Diagnostics Inc., the U.