Oral methotrexate and risk of unintentional overdose due to medication errors

Oral methotrexate and risk of unintentional overdose due to medication errors

Oral dosage forms of methotrexate are used in the treatment of inflammatory autoimmune diseases as a low single dose once weekly. Accidentally taking a dose daily that should be taken weekly can result in an overdose with serious consequences and possibly even be fatal.

Methotrexate, overdose, pancytopenia, dose adjustment Rheumatoid arthritis, palliative therapy, stomatitis

Incident data


Case: 2022

Age: 72 years

Sex: Female

Medicinal product: Methotrexate and Endoxan®

Active substances: Methotrexate and cyclophosphamide

Indication: Palliative therapy

ADRs: accidental overdose, pancytopenia, stomatitis, increase in liver enzymes

Outcome: recovered

A female patient with stage IV breast cancer with bone, liver and peritoneal metastases was prescribed outpatient palliative oral chemotherapy with methotrexate and cyclophosphamide. Methotrexate was prescribed at a dosage of 2 x 2.5 mg 1-0-1 on Tuesdays and Fridays.

The patient mistakenly took 2 x 2.5 mg methotrexate per day for eight consecutive days. She had to be admitted as an emergency due to mucositis, pancytopenia and liver toxicity.

The chemotherapy was discontinued, a platelet concentrate was transfused and the bone marrow was stimulated with Filgrastim®, which resulted in a favourable outcome.

Case: 2023

Age: 80 years

Sex: Male

Medicinal product: Methotrexate 20 mg/week p.o.

Active substances: Methotrexate

Indication: Seropositive rheumatoid arthritis

ADR: Neutropenia, anaemia, thrombocytopenia, gastrointestinal mucositis, accidental overdose

Outcome: improved

Following admission to hospital for a subdural haematoma with surgical drainage, relatives noticed a decline in the patient’s general condition with loss of appetite one day after returning home. On readmission, the initial examination revealed severe mucositis of the digestive tract (oral mucositis, odynophagia) and laboratory tests identified pancytopenia.

The records of the previous hospitalisation showed that methotrexate 20 mg had been prescribed once a day instead of once a week following the surgical procedure.

Following treatment with Filgrastim® and folinic acid, the patient’s condition improved and he was able to be discharged and return home.

Summary and recommendation

As far back as 2012, Swissmedic and the Swiss Patient Safety Foundation drew attention to serious incidents caused by daily rather than weekly administration of low-dose methotrexate to patients with rheumatoid arthritis and psoriasis.

In these indications, the normal weekly dose is 10-15 mg. If such a dose is taken daily, the result is severe poisoning that can sometimes be fatal. Although errors involving daily instead of weekly administration of methotrexate have been known for a long time, there are still avoidable and serious cases of incorrect daily doses.

Methotrexate-related errors occur at all levels of the interfaces in the care process: prescribing by doctors, administration by carers or family members, dispensing in pharmacies or administration by patients, incorrect or incomplete communication. It is vital that healthcare professionals carefully instruct and monitor the patients concerned. In the event that the medicinal product is nonetheless taken too frequently, it is important to recognise the symptoms of an overdose.

At the international level, a number of organisations have published useful recommendations for the prevention of overdoses involving methotrexate. These recommendations should also be implemented consistently in Switzerland with the involvement of all healthcare providers. The warnings in the medicinal product information and in the publications on medicinal product safety (DHPC) must be strictly observed. Patients must be made aware of how to take the product correctly.

Statutory duty of healthcare professionals to report adverse drug reactions (ADRs)

In Switzerland, healthcare professionals who are authorised to dispense or administer medicinal products are obligated to report severe and/or previously unknown side effects. Reports to Swissmedic can be entered and sent in the Electronic Vigilance Reporting Portal “ElViS” (ElViS login).


  • Quick-Alert N. 28 (V2): Sovradosaggio di metotressato, 29.09.2023.
  • Brühwiler LD, Gresch SJ, Schwappach DLB. Implementation status of safety measures to prevent errors with non-oncologic methotrexate: surveys in community and hospital pharmacies. Int J Clin Pharm. 2023 Jun;45(3):739-747.
  • Institute for Safe Medicine Practices (ISMP). ISMP Targeted Medication Safety Best Practices for Hospitals. https://www.ismp.org/sites/default/files/attachments/2020-02/2020-2021%20TMSBP-%20FINAL_1.pdf. Published February 21, 2020. Accessed January 12, 2022.

Supplementary information