Gadolinium-containing contrast agents
- Procedure started
- Under evaluation
- PRAC recommendation
- CHMP opinion
- European Commission final decision
Table of contents
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,
confirming 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.
Product | Type (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 | |
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
Gadolinium Article-31 referral - Annex I (PDF/313.02 KB)
First published: 18/03/2016
Last updated: 26/04/2016
EMA/207286/2016
Gadolinium Article-31 referral – PRAC list of questions (PDF/108.54 KB)
First published: 18/03/2016
Last updated: 18/03/2016
EMA/PRAC/188631/2016
Gadolinium Article-31 referral - Review started (PDF/88.92 KB)
First published: 18/03/2016
Last updated: 18/03/2016
EMA/200364/2016
Gadolinium Article-31 referral – Timetable for the procedure (PDF/79.16 KB)
First published: 18/03/2016
Last updated: 30/05/2017
EMA/PRAC/195601/2016 Rev.7
Gadolinium Article-31 referral – Notification (PDF/48.19 KB)
First published: 18/03/2016
Last updated: 18/03/2016
Recommendation provided by Pharmacovigilance Risk Assessment Committee
Gadolinium Article-31 referral – PRAC confirms restrictions on the use of linear gadolinium agents (PDF/67.88 KB)
First published: 07/07/2017
Last updated: 07/07/2017
EMA/424715/2017
Gadolinium Article-31 referral – PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension for some marketing authorisations (PDF/72.58 KB)
First published: 10/03/2017
Last updated: 07/04/2017
EMA/157486/2017
Opinion provided by Committee for Medicinal Products for Human Use
Gadolinium Article-31 referral – Annex III (PDF/68.69 KB)
First published: 21/07/2017
Last updated: 21/07/2017
Gadolinium Article-31 referral – EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans (PDF/85.46 KB)
First published: 21/07/2017
Last updated: 21/07/2017
EMA/457616/2017
European Commission final decision
Gadolinium Article-31 referral – Annex III (PDF/72.49 KB)
First published: 19/12/2017
Last updated: 19/12/2017
Gadolinium Article-31 referral – Annex IV (PDF/26.28 KB)
First published: 19/12/2017
Last updated: 19/12/2017
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
Gadolinium Article-31 referral – Annex II (PDF/135.69 KB)
First published: 19/12/2017
Last updated: 19/12/2017
Gadolinium Article-31 referral – CHMP divergent positions (PDF/59.4 KB)
First published: 19/12/2017
Last updated: 19/12/2017
Gadolinium Article-31 referral – Annex I (PDF/305.84 KB)
First published: 19/12/2017
Last updated: 19/12/2017
Gadolinium Article-31 referral - Assessment report (PDF/1.34 MB)
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
News
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21/07/2017
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21/07/2017
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07/07/2017
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07/04/2017
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10/03/2017
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10/03/2017
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13/01/2017
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28/10/2016
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30/09/2016
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02/09/2016
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10/06/2016
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13/05/2016
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15/04/2016
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18/03/2016