Methotrexate — Rapid | Doctor’s Passport

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.
Before treatment check FBC, ALT or AST and albumin, creatinine and eGFR, weight, pregnancy, alcohol and liver risk, lung history and hepatitis, HIV or TB risk as clinically indicated.
Initial monitoring is frequent and risk-adapted: commonly every two weeks until the dose is stable for six weeks, monthly for three months, then at least every twelve weeks when stable, following the agreed specialist protocol.
Trend matters more than a single normal-range result. Falling neutrophils or albumin, rising MCV or transaminases and declining filtration should trigger early review before an absolute stop threshold is crossed.
Never prescribe trimethoprim or co-trimoxazole with methotrexate unless a specialist deliberately manages an exceptional indication because severe and sometimes delayed marrow suppression can occur.
Hold methotrexate during a serious infection and obtain specialist advice about restart; mild self-limiting illness does not need an improvised prolonged interruption.
Methotrexate is incompatible with pregnancy and breastfeeding. BSR advises stopping low-dose treatment at least one month before planned maternal conception; paternal doses of 25 mg weekly or less are compatible.
If nausea, poor absorption or inadequate response limits oral treatment, split oral dosing over one day or change to once-weekly subcutaneous administration under specialist direction before declaring failure.

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.

Fever, sore throat, mouth ulceration, bruising, bleeding or severe diarrhoea suggests marrow or mucosal toxicity and requires immediate withholding and blood counts.

New dry cough, dyspnoea, hypoxaemia or diffuse pulmonary shadowing may represent methotrexate pneumonitis, opportunistic infection or inflammatory lung disease.

Jaundice, marked transaminase rise, falling albumin or right-upper-quadrant symptoms requires interruption and assessment for drug, alcohol, metabolic and viral liver injury.

Vomiting, dehydration, oliguria or a sudden eGFR fall can turn a previously tolerated weekly dose toxic by reducing renal clearance.

Pregnancy or conception within the advised washout interval requires immediate cessation, folic acid 5 mg daily and urgent rheumatology, obstetric and fetal-medicine advice.

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.

Pneumonitis pattern

Subacute dry cough, breathlessness, fever, hypoxaemia and diffuse interstitial change during treatment is methotrexate pneumonitis until infection and other lung disease are excluded.

Investigation priorities

First-line baseline FBC, liver and renal profileFirst stepFirst line

Confirm marrow reserve, liver status and renal clearance before the first dose.

Management branches

First-line initiationMake weekly dosing unambiguous

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.
Arrange named responsibility for early FBC, liver and renal monitoring and a contact route for mouth ulcers, fever, bruising, dyspnoea or dosing error.

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.Never daily. Avoid pregnancy, breastfeeding and severe renal or hepatic disease; monitor marrow, liver, kidney, infection and lung toxicity and avoid trimethoprim or co-trimoxazole.

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.The injection remains systemic methotrexate with the same marrow, hepatic, renal, pulmonary, infection and reproductive risks; train handling and sharps disposal and prevent oral duplication.

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