A statement from the Pharmaco Vigilance Service:

"You may be aware that the European Medicines Agency (EMA) has recently completed a review of the occurrence of dosing errors which resulted in patients taking methotrexate for inflammatory diseases daily instead of once weekly. From this review have come a number of recommendations for European member states to implement in order to minimise the risk of these errors occurring.

As you'll know, this is an issue which has been assessed in the UK in the past. In England, this is included in NHS Improvement's list of ‘never events'. Work has been done over many years to minimise this risk which has included the provision of educational materials for patients and updates to prescribing systems to prompt warnings when methotrexate is being prescribed.

These measures are deemed to have been very effective and the PRAC recommendations are aimed at complimenting existing measures in place in European member states and continuing to reduce these errors across Europe.

To summarise, the recommendations for implementation in the UK are as follows:

  • Product information updates:
    • should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy
    • the prescriber should ensure patients/carers are able to comply with once-weekly dosing
    • warning about once-weekly dosing and consequences of dosing errors
    • deletion of wording recommending dividing daily dose
  • Replacement of bottle packaging with blister packaging
  • A warning on the outer packaging ‒ including a place to write the day of the week to take methotrexate
  • A warning on the blister packaging
  • Implementation of a patient card
  • Educational materials for healthcare professionals
  • Direct Healthcare Professional Communication to remind healthcare professionals of the risk and inform them of the updated measures to minimize dosing errors  


While waiting for a final decision from the European Commission on the recommendations, we held a meeting with relevant organisations to discuss the recommendations and how they might best be implemented in light of what is already in place in the UK. From this meeting as well as other channels, we have received feedback on the recommendations, particularly regarding the line in the product information “Methotrexate should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy.”

Some methotrexate products in the UK include this wording already, so the action is a harmonisation in the statutory product information across all products rather than an introduction of new advice. This harmonisation is not intended to change who can currently prescribe methotrexate in the UK.

We have also received feedback that there may be some concern around how the expertise necessary to prescribe methotrexate would be defined. From MHRA’s standpoint, this is to express that prescribers should be aware of the benefits and risks of methotrexate treatment and have the necessary professional competence to safely prescribe it. Further definition of the competency required for methotrexate prescribing would be outside of the domain of the agency.

Communications on these recommendations are being planned and so we wanted to give you advance notice of these activities."


Scientific Assessor

Vigilance and Risk Management of Medicines

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