Antifolate / DMARD / cytotoxic antimetabolite
Methotrexate
Antifolate used at low weekly oral doses for inflammatory disease (rheumatoid arthritis, psoriasis, Crohn's) and at high doses as cytotoxic chemotherapy. Inadvertent daily dosing has caused fatal toxicity.
Indications
- Rheumatoid arthritis (first-line conventional DMARD)
- Severe psoriasis and psoriatic arthritis
- Crohn's disease maintenance
- Ectopic pregnancy (medical management)
- Various malignancies at high dose (ALL, choriocarcinoma, osteosarcoma)
Dosing
Inflammatory disease (low dose)
Once-weekly only. Typical RA starting dose 7.5–15 mg PO once weekly, titrated to maintenance 15–25 mg weekly. Always specify the day of the week on the prescription.
Folic acid co-prescription
Folic acid 5 mg once weekly (NOT on the methotrexate day) is co-prescribed to reduce GI and haematological toxicity in most low-dose regimens.
Strengths
Tablets are 2.5 mg only in UK general practice (10 mg tablets are available but are an avoid-where-possible strength to reduce dispensing errors). Always dispense one strength per patient.
Always confirm doses against the current BNF — this summary is for study, not prescribing.
Monitoring
- FBC, U&E, LFTs before initiation; then weekly until stable, then every 2–3 months
- Symptom check for shortness of breath, persistent cough (pneumonitis)
- Mouth ulcers, sore throat, unusual bruising → urgent FBC
- Pregnancy testing in women of childbearing potential before initiation
Contraindications
- Pregnancy — teratogenic and abortifacient
- Breastfeeding
- Severe hepatic or renal impairment
- Active infection, bone marrow failure, immunodeficiency
- Active or recent peptic ulcer disease
Important interactions
- NSAIDs and aspirin — reduce methotrexate clearance, increase toxicity (especially at chemotherapy doses; usually safe at low doses with care)
- Trimethoprim and co-trimoxazole — additive antifolate effect → bone-marrow suppression. Avoid concurrent use
- Probenecid, penicillins — can raise methotrexate levels
- Live vaccines — avoid (immunosuppression)
- Alcohol — additive hepatotoxicity, limit intake
Counselling points
- Take ONCE A WEEK on the same agreed day — never daily
- Take folic acid on a different day to minimise toxicity
- Carry your methotrexate monitoring booklet to every appointment
- Effective contraception during and for at least 6 months after stopping (men and women per current BNF / SmPC)
- Avoid trimethoprim-containing antibiotics — tell any prescriber you are on methotrexate
- Limit alcohol; report cough, breathlessness, mouth ulcers, or unusual bruising urgently
Red flags
- Daily dosing error — risk of pancytopenia and death; review and treat with folinic acid (calcium folinate) per Toxbase / poisons centre
- Pneumonitis — non-productive cough and breathlessness; stop drug and refer urgently
- Pregnancy on methotrexate — refer to obstetrics urgently
Practice for the CRA
Drug-specific questions, calculations, and full mock exams aligned to the GPhC Common Registration Assessment.