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

The cartilage in this MRI scan of a knee is colorized to show greater contrast between shades of gray.

The cartilage in this MRI scan of a knee is colorized to show greater contrast between shades of gray. Image courtesy of Kundu et al. (2020) PNAS

News | Artificial Intelligence | September 22, 2020
September 22, 2020 — Researchers at the University of Pitts...
A new report, Magnetic Resonance Imaging Equipment Market Size, Share & Industry Analysis, conducted by Fortune Business Insights, states that the magnetic resonance imaging (MRI) equipment market reached $7.24 billion in 2019 and is projected to reach $11.36 billion by 2027

Image courtesy of Siemens Healthineers

Feature | Magnetic Resonance Imaging (MRI) | September 21, 2020 | By Melinda Taschetta-Millane
A new report,...
Figure 1. Doppler flows in subpleural consolidation shows smoothly dilated branching arteries

Figure 1. Doppler flows in subpleural consolidation shows smoothly dilated branching arteries 

Feature | Radiology Imaging | September 17, 2020 | By Robert Bard, M.D. PC, DABR, FASLM
COVID-19 is routinely studied using...
 A cardiac MRI is effective in identifying inflammation of the heart muscle in athletes and can help determine when those who have recovered from COVID-19 can safely return to play in competitive sports, according to a new study by researchers at The Ohio State University Wexner Medical Center.

Getty Images

News | Cardiac Imaging | September 14, 2020
September 14, 2020 — A...
All intensive care unit equipment, including ventilators, pumps, and monitoring devices, as well as the point-of-care magnetic resonance image operator and bedside nurse, remained in the room. All equipment was operational during scanning.

All intensive care unit equipment, including ventilators, pumps, and monitoring devices, as well as the point-of-care magnetic resonance image operator and bedside nurse, remained in the room. All equipment was operational during scanning. Image courtesy of JAMA Neurology

News | Magnetic Resonance Imaging (MRI) | September 11, 2020
September 11, 2020 — A portable, low-field...
Six months after deployment, the no-show rate of the predictive model was 15.9%, compared with 19.3% in the preceding 12-month preintervention period — corresponding to a 17.2% improvement from the baseline no-show rate (p < 0.0001). The no-show rates of contactable and noncontactable patients in the group at high risk of appointment no-shows as predicted by the model were 17.5% and 40.3%, respectively (p < 0.0001).

Weekly outpatient MRI appointment no-show rates for 1 year before (19.3%) and 6 months after (15.9%) implementation of intervention measures in March 2019, as guided by XGBoost prediction model. Squares denote data points. Courtesy of the  American Roentgen Ray Society (ARRS), American Journal of Roentgenology (AJR)

News | Artificial Intelligence | September 10, 2020
September 10, 2020 — According to ARRS’
Vantage Galan with Advanced intelligent Clear-IQ Engine (AiCE) provides high-quality images and fast exam times

Coronal orbit images: Left original and right with AiCE.

News | Magnetic Resonance Imaging (MRI) | September 09, 2020
September 9, 2020
the Contrast Media Injectors Market is estimated to be USD 1.3 billion in 2020 and  projected to reach $1.9B by 2025, at a CAGR of 7.4% between 2020 and 2025

Getty Images

News | Contrast Media Injectors | September 02, 2020
September 2, 2020 — According to the new market research report "...
The global pediatric imaging market size is expected to reach $12.2 billion by 2027, registering a CAGR of 7.6% over the forecast period, according to a new report by Grand View Research, Inc.

Getty Images

News | Pediatric Imaging | August 26, 2020
August 26, 2020 — The global ...
AI-Rad Companion Prostate MR for Biopsy Support segments prostate for targeted biopsy under MRI and ultrasound fusion imaging

Image courtesy of Clinica Universidad de Navarra, Spain

News | Artificial Intelligence | August 19, 2020
August 19, 2020 — The Food and Drug Administration (FDA) has cleared two additional...