Gadolinium-containing contrast agents

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview

EMA's final opinion confirms restrictions on use of linear gadolinium agents in body scans

Recommendations conclude EMA's scientific review of gadolinium deposition in brain and other tissues

On 20 July 2017, the European Medicines Agency (EMA) concluded its review of gadolinium contrast agents, PDF iconconfirming recommendations to restrict the use of some linear gadolinium agents used in MRI body scans and to suspend the authorisations of others.

The recommendations – confirmed by EMA's Committee for Medicinal Products for Human Use (CHMP) – followed a review that found that gadolinium deposition occurs in brain tissues following use of gadolinium contrast agents.

There is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions and suspensions for some intravenous linear agents in order to prevent any risks that could potentially be associated with gadolinium brain deposition.

The intravenous linear agents gadoxetic acid and gadobenic acid can continue to be used for liver scans because they are taken up in the liver and meet an important diagnostic need. In addition, gadopentetic acid given intra-articularly (into the joint) can continue to be used for joint scans because the dose of gadolinium used for joint injections is very low.

All other intravenous linear products (gadodiamide, gadopentetic acid and gadoversetamide) should be suspended in the EU.

Another class of gadolinium agents known as macrocyclic agents (gadobutrol, gadoteric acid and gadoteridol) are more stable and have a lower propensity to release gadolinium than linear agents. These products can continue to be used in their current indications but in the lowest doses that enhance images sufficiently and only when unenhanced body scans are not suitable.

The suspensions or restrictions on linear agents can be lifted if the companies concerned provide evidence of new benefits in an identified patient group that outweigh the risk of brain deposition or if the companies can modify their products so they do not release gadolinium significantly or cause its retention in tissues.

EMA's scientific review of gadolinium deposition in brain and other tissues is now concluded. The final recommendations have been sent to the European Commission, which issued a final legally binding decision applicable in all EU Member States.

ProductType (formulation)Recommendation

Artirem / Dotarem (gadoteric acid)

macrocyclic (i.v.)

maintain

Artirem / Dotarem (gadoteric acid)

macrocyclic (intra-articular)

maintain

Gadovist (gadobutrol)

macrocyclic (i.v.)

maintain

Magnevist (gadopentetic acid)

linear (intra-articular)

maintain

Magnevist (gadopentetic acid)

linear (i.v.)

suspend

Multihance (gadobenic acid)

linear (i.v.)

restrict use to liver scans

Omniscan (gadodiamide)

linear (i.v.)

suspend

Optimark (gadoversetamide)

linear (i.v.)

suspend

Primovist (gadoxetic acid)

linear (i.v.)

maintain

Prohance (gadoteridol)macrocyclic (i.v.)maintain

Key facts

About this medicine
Approved name
Gadolinium-containing contrast agents
International non-proprietary name (INN) or common name
gadobenic acid / gadobutrol / gadodiamide / gadopentetic acid / gadoteric acid / gadoteridol / gadoversetamide / gadoxetic acid
Associated names
Optimark
Class
-
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1437
Type
Article 31 referrals

This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally and nationally authorised products (mixed)
Key dates and outcomes
Procedure start date
17/03/2016
PRAC recommendation date
06/07/2017
CHMP opinion/CMDh position date
20/07/2017
EC decision date
23/11/2017
Outcome
Suspension

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    Gadolinium Article-31 referral – EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans (PDF/104.44 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017
    EMA/625317/2017

  • List item

    Gadolinium Article-31 referral – Annex III (PDF/72.49 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017

  • List item

    Gadolinium Article-31 referral – Annex IV (PDF/26.28 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017

  • List item

    Gadolinium Article-31 referral – EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans (PDF/104.44 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017
    EMA/625317/2017

  • List item

    Gadolinium Article-31 referral – Annex II (PDF/135.69 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017

  • List item

    Gadolinium Article-31 referral – CHMP divergent positions (PDF/59.4 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017

  • List item

    Gadolinium Article-31 referral – Annex I (PDF/305.84 KB)


    First published: 19/12/2017
    Last updated: 19/12/2017

  • List item

    Gadolinium Article-31 referral - Assessment report (PDF/1.34 MB)

    Adopted

    First published: 04/12/2017
    Last updated: 04/12/2017
    EMA/411650/2017

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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