MSK & Rheumatology/Antifolate DMARD

Methotrexate

also: MTX · DMARD · folate antagonist

Overview

The anchor disease-modifying drug for rheumatoid arthritis (and used in psoriasis, IBD, ectopic, chemo). The WEEKLY dosing, folic acid, and monitoring are the safety essentials — and a classic fatal prescribing error.

Mechanism

Inhibits dihydrofolate reductase → ↓folate → ↓DNA synthesis in rapidly dividing cells (immunosuppressive/antiproliferative). Folic acid (on a DIFFERENT day) reduces toxicity.

Indications

Rheumatoid arthritis (first-line DMARD)
Psoriasis / psoriatic arthritis (cross-ref derm)
Crohn's; ectopic pregnancy; malignancy

Adverse effects

Myelosuppressionserious

Monitor FBC; worse with trimethoprim/co-trimoxazole (both antifolates).

Hepatotoxicity (monitor LFTs); pulmonary fibrosis/pneumonitisserious

Mucositis, GI upsetcommon

Teratogenic / abortifacientserious

Effective contraception; stop ~3–6 months before conception (both sexes).

Cautions & contraindications

WEEKLY dosing — never dailyall

Daily methotrexate dosing is a classic fatal error (fatal marrow toxicity).

Methotrexate + trimethoprim/co-trimoxazoleall

Additive antifolate → severe myelosuppression.

Pregnancy / significant liver or renal diseasepregnancy

Interactions

Trimethoprim/co-trimoxazole, NSAIDs, penicillins (↑MTX levels/toxicity)

Monitoring & kinetics

FBC, U&E, LFTs (regularly); CXR/respiratory symptoms (pneumonitis),Co-prescribe folic acid (on a non-MTX day)

Oral/SC ONCE WEEKLY. The weekly rule + folic acid + monitoring define safe use.

Choosing it

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Source: NICE NG100 — Rheumatoid arthritis · BNF — Methotrexate