Methotrexate containing medicinal products

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



EMA reviewing risk of dosing errors with methotrexate

Review prompted by continued reports of overdose

The European Medicines Agency (EMA) has started a review of the risk of dosing errors with methotrexate medicines.

When used for inflammatory diseases, such as arthritis and psoriasis, methotrexate is taken once a week whereas for some types of cancer, the dose is higher and the medicine is used more frequently. Mistakes have led to some patients incorrectly receiving a dose every day instead of every week. As a result, patients have received too much of the medicine, with serious consequences in some cases.

The risk of dosing errors with methotrexate has been recognised for many years and several measures are already in place in some EU countries to reduce this risk, including the use of visual reminders on the medicine packs. However, a recent assessment1 found that serious adverse events related to overdose, including fatalities, are still occurring. The Spanish medicines regulator, AEMPS, therefore asked EMA to further investigate the reasons why dosing errors continue to occur in order to identify measures to prevent them.

EMA's Pharmacovigilance Risk Assessment Committee (PRAC) will now examine the available evidence and recommend whether further measures are needed to minimise the risk of dosing errors. The PRAC will also take into account the work of bodies specialising in patient safety.

1 This was in the context of a routine benefit-risk assessment, known as a periodic safety update report (PSUR) assessment.

Key facts

About this medicine
Approved name
Methotrexate containing medicinal products
International non-proprietary name (INN) or common name


Associated names
  • Nordimet
  • Jylamvo
About this procedure
Current status
Under evaluation
Reference number
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
Authorisation model
Centrally and nationally authorised products (mixed)
Key dates and outcomes
Procedure start date

All documents

Procedure started

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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