Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.
2 min synopsisUK scopeSources checked 27 Aug 2026Clinical review pending
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Methotrexate toxicity or dosing error
Daily ingestion instead of weekly dosing, severe mouth ulcers, fever, bruising, bleeding, profound diarrhoea, breathlessness or renal deterioration can herald fatal pancytopenia, mucosal injury, infection or pneumonitis.
Action: Stop methotrexate and arrange same-day hospital assessment with FBC, renal and liver profiles and specialist toxicology or haematology advice; treat sepsis, do not wait for the next monitoring appointment, and use folinic-acid rescue and enhanced elimination only under the acute specialist protocol.
Synopsis
Prescribe low-dose once-weekly methotrexate safely for inflammatory rheumatic disease, combine it with folate and disease-specific treatment, and detect dosing errors, marrow, liver, renal, lung, infection and reproductive toxicity early.
Low-dose methotrexate for rheumatic disease is taken once weekly, never once daily; write the day in words, keep tablet strength consistent and confirm understanding at every handover.
A usual adult starting dose is 7.5–15 mg once weekly orally or subcutaneously, increased in 2.5–5 mg steps according to response and monitoring to a usual maximum of 25 mg once weekly.
Co-prescribe folic acid at least 5 mg once weekly on a different day; increase or redistribute folate for adverse effects under the specialist plan without placing it on the methotrexate day.
Key red flags
Any confirmed or possible daily-for-weekly dosing error requires urgent assessment even when the patient initially feels well because cytopenia and mucositis may be delayed.
Mucosal and marrow toxicity
Painful oral ulcers, sore throat, fever, bruising, bleeding, pallor or profound fatigue may precede or accompany cytopenia and require same-day interruption and FBC.
Investigation priorities
01
First-line baseline FBC, liver and renal profileFirst stepFirst line
Confirm marrow reserve, liver status and renal clearance before the first dose.
Methotrexate is selected as a conventional DMARD and baseline safety assessment is satisfactory.
Agree one weekly day, prescribe 7.5–15 mg once weekly using one tablet strength where possible and provide written plus verbal schedule confirmation.
Prescribe folic acid at least 5 mg once weekly on a different day and document contraception, vaccines, alcohol and infection advice.
Key medicines
Methotrexate oralStart 7.5–15 mg orally once weekly on one named day; increase by 2.5–5 mg steps according to response and laboratory monitoring to a usual maximum of 25 mg once weekly.
Methotrexate subcutaneousGive the total prescribed dose subcutaneously once weekly on one named day, usually using the same milligram weekly dose as oral treatment when switching, with specialist titration up to 25 mg weekly.
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.