Methotrexate: EMA is looking for ways to prevent overdose

Methotrexate: EMA is looking for ways to prevent overdose


Monday, April 16, 2018

London – The unusual once-weekly dosing of methotrexate in the treatment of many autoimmune diseases leads again and again to dosage errors that are now the subject of a Risk assessment process the European Medicines Agency (EMA).

Most medications need to be taken daily. It is routine for doctors to write a once-daily dose on the prescription, and most patients are used to taking their pills daily. In methotrexate this can be fatal. The drug, which was originally developed as a high-dose cytostatic drug for cancer therapy, is now used at a lower dose more often for the treatment of autoimmune diseases, where it should prevent the progression of tissue destruction as an immunosuppressive agent.

Methotrexate is the most commonly prescribed basic drug or DMARD (for disease-modifying anti-rheumatic drug). For autoimmune diseases, once a week dosing is the norm. It can be given as an intravenous, subcutaneous or intramuscular injection to the doctor. However, the patient may be instructed to take the medication once a week.

This always leads to fatal revenue errors. There are numerous case reports in the literature in which patients inadvertently ingested the medication on a daily basis. The overdose then leads relatively quickly, sometimes within a few days, to mucosal damage in the gastrointestinal tract, to liver damage, to changes in the blood count, to increased susceptibility to sepsis and in the worst case to death.

By no means only the patients are guilty. There are also cases in which doctors have accidentally prescribed the daily intake or communication has failed, for example, if the doctor verbally “on Mondays” order, but the patient has “always morning” understood.

There are already a number of precautionary measures to minimize the risk, including the introduction of a visual warning on the outer packaging of the drug, which has been introduced in many EU countries. Nevertheless, a recent EMA periodic safety report has shown that serious adverse events, including deaths, still occur.

The Spanish Medicines Agency, AEMPS, has therefore asked the EMA to further investigate the causes of the occurrence of dosage errors and to identify what prevention measures should be taken.

The EMA has now mandated the Pharmacovigilance Risk Assessment Committee (PRAC) to explore the scale of the problem and then look for ways to prevent overdosing in the future. Ideas have not yet been communicated. © warmth /

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