PRAC Proposes New Measures to Avoid Methotrexate Dosing Errors

Megan Brooks


July 12, 2019

The European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended new measures to reduce the risk of dosing errors with medicines containing methotrexate

"Mistakes in prescribing or dispensing methotrexate as well as misunderstandings of the dosing schedule have led to patients taking the medicine daily instead of weekly for inflammatory diseases, with serious consequences, including fatalities," the EMA explains in a statement

The new measures include restricting who can prescribe these medicines, making warnings on the packaging more prominent, and providing educational materials for patients and healthcare providers. To help patients follow the once-weekly dosing, methotrexate tablets for weekly use will be provided in blister packs instead of bottles.

Methotrexate is used to treat various inflammatory conditions, such as arthritis, psoriasis, Crohn's disease, and some cancers, such as acute lymphoblastic leukemia. Methotrexate can be taken by mouth or given by injection. For inflammatory diseases, methotrexate is taken once a week; higher doses given more frequently may be used for the treatment of cancer.

The risk of dosing errors with methotrexate-containing medicines is well known. However, despite several measures already in place, these errors continue to occur. This led the EMA to launch a review of the problem last year, as reported by Medscape Medical News.

The PRAC examined the available evidence and recommended additional measures to reduce dosing errors so that the benefits of methotrexate-containing medicines continue to outweigh their risks. The following measures were agreed to after consultation with patients and healthcare professionals:

  • Only clinicians with expertise in using methotrexate-containing medicines should prescribe them.

  • Healthcare professionals should ensure that patients or carers are able to follow the once-weekly dosing schedule.

  • To avoid confusion, recommendations to split the dose should be deleted from the product information for the tablet formulation.

  • Packaging for all methotrexate-containing medicines for once-weekly use will include a prominent reminder of how the medicine should be used.

  • A patient card emphasizing the weekly dosing for inflammatory diseases should be provided with oral medicines.

  • Healthcare professionals will be provided with educational materials for oral medicines and should counsel patients accordingly.

  • Make tablets available in blister packs only (not bottles or tubes) to help patients follow the once-weekly dosing.

The PRAC recommendations will now be sent to the Committee for Medicinal Products for Human Use (CHMP), which will adopt an opinion.

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