PRAC July 2019 – EMA recommends new measures to avoid dosing errors with methotrexate and has started a review of meningioma risk with cyproterone medicines

During its meeting of July 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended new measures to avoid dosing errors with methotrexate. Furthermore, the PRAC started a review of meningioma risk with cyproterone medicines

New measures to avoid dosing errors with methotrexate

The PRAC is recommending new measures to avoid dosing errors that have led to some patients incorrectly taking methotrexate – containing medicines daily instead of weekly.

The new measures include:

  • restricting who can prescribe these medicines;
  • making warnings on the packaging more prominent;
  • providing educational materials for patients and healthcare professionals.

In addition, to help patients follow the once-weekly dosing, methotrexate tablets for weekly use will be provided in blister packs and not in bottles (or tubes).

Methotrexate is used for treating both inflammatory diseases and cancers. When used for inflammatory diseases, such as arthritis and psoriasis, it is taken once a week but for some types of cancer, a much higher dosage is needed and the medicine is taken more frequently. 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 risk of dosing errors with methotrexate – containing medicines is well known. However, despite several measures already in place, these errors continue to be reported.

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


Measures to prevent dosing errors with methotrexate

  • Only doctors with expertise in using methotrexate – containing medicines to prescribe them.
  • Healthcare professionals to 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 to include a prominent reminder of how the medicine should be used.
  • Patient card emphasising the weekly dosing for inflammatory diseases to be provided with oral medicines.
  • Healthcare professionals to be provided with educational materials for oral medicines and to counsel patients accordingly.
  • Tablets to be available in blister packs instead of bottles (or tubes) in order 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.

Healthcare professionals will be informed in writing of the above changes. Patients who have any concerns about their medicine in the meantime should discuss them with their doctor or pharmacist.

The following methotrexate – containing medicines are authorised and marketed in Belgium : Emthexate, Ledertrexate, Methotrexate Accord Healthcare, Metoject.

More information is available on the EMA website.


Review of meningioma risk with cyproterone medicines

EMA has started a review of medicines containing cyproterone, which are used for treating a range of conditions, including excessive hair growth, prostate cancer and acne, as well as in hormone replacement therapy.

The review will look into the risk of meningioma, a rare, usually non-cancerous tumour of the membranes covering the brain and spinal cord. The risk of meningioma with cyproterone daily doses of  10 mg or more has been known since 2008 and information was included in the prescribing information for these medicines along with a warning that cyproterone should not be used in people who have or have had a meningioma tumour. However, there was no information at the time on the magnitude of the risk and how the risk could change with different doses.

A recent study in France has now suggested that the risk of meningioma, although still very low, may be greater in those taking high doses of cyproterone for a long period. The study also showed that after patients had stopped cyproterone treatment for at least one year, the risk of developing these tumours was much reduced but remained slightly higher than usual.

Due to their location in and around the brain and spinal cord, meningiomas can cause serious problems. The French medicines authority has therefore asked EMA to investigate this risk, taking into account all the latest data.

The PRAC will now examine the available evidence and make recommendations as to whether the marketing authorisations for cyproterone-containing medicines should be amended across the EU.

The following cyproterone – containing medicines are authorised and marketed in Belgium: Androcur, Claudia, Climen, Daphne, Daphne Continu, Diane, Elisamylan.

More information is available on the EMA website.

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