Oral methotrexate can cause serious side effects in the event of overdose. Despite the measures put in place, cases of accidental overdose continue to be reported. Most cases result from taking the medicine too often compared to the prescription. For the treatment of inflammatory diseases, oral methotrexate should only be taken once a week, always on the same day.
Methotrexate (Ledertrexate in Belgium) is used to treat both inflammatory diseases and some cancers. When used for inflammatory diseases, including rheumatoid polyarthritis or psoriasis, it should be taken once a week. For some types of cancer, the patient needs a much higher dose and takes the medicine more frequently. Errors 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.
In 2019, the European Medicines Agency (EMA) recommended new measures to prevent serious and potentially fatal dosing errors with methotrexate. These measures include clearly visible warnings on the outer and inner packaging of the medicine and the provision of educational material for patients and healthcare professionals.
Despite these recommendations, medication errors involving oral methotrexate still occur frequently.
Most cases of overdose are linked to the inadvertent administration of a daily dose instead of the indicated weekly dose. Poor organisation of pill boxes is sometimes reported. Cases of overdose have also been observed in patients who have mistaken methotrexate for folic acid, which should be taken simultaneously (one day apart).
Patients should be informed of the importance of adhering to once-weekly dosing. Prescribers must ensure that patients understand that methotrexate should only be taken once a week.
Information for healthcare professionals
To reduce the risk of methotrexate overdose, healthcare professionals prescribing or dispensing methotrexate for inflammatory diseases must:
• provide the patient/caregiver with full and clear instructions on the weekly single dose;
• carefully check with each new prescription/dispensing that the patient/caregiver understands that the medicine must be used once a week;
• decide with the patient/caregiver which day of the week the patient must take methotrexate;
• inform the patient/caregiver of the signs of overdose and ask him or her to consult a doctor rapidly in the event of a suspected overdose;
• when a prescription renewal is requested, the doctor should ask the patient how often they take methotrexate, in order to detect any dosing errors quickly. As part of the provision of pharmaceutical care, the pharmacist checks the dispensing history in the pharmacy and in the Shared Patient Record (if available) to ensure that the quantities dispensed correspond to the once-weekly frequency of use.
Information for patients
• To prevent an overdose of methotrexate for the treatment of inflammatory diseases such as psoriasis and rheumatoid polyarthritis, it is essential to take these medicines only once a week.
• Overdose can lead to serious side effects and can be life-threatening.
• Be alert to symptoms of overdose. Examples are sore throat, fever, mouth ulcers, diarrhoea, vomiting, skin rashes, bleeding or unusual weakness.
• Seek immediate medical attention if you think you have taken more than the prescribed dose.
• An information card available in the medicine packaging reminds you of the dose of methotrexate to take and the symptoms of overdose. Keep this card and show it to any healthcare professionals you consult and/or to your caregiver to inform them of this treatment.
How to notify a medication error?
• Errors with no adverse reactions
Potential or actual errors with no adverse reactions can be reported to medication-errors@fagg-afmps.be.
• Errors with adverse reactions
If the error led to an adverse reaction, the classic reporting system should be used and the context of the medication error should be described, via www.famhp.be/en/side_effect.