Conventional DMARDs · Pain & inflammation
Methotrexate
MTX · Rheumatrex® · Metoject®(brand names vary by market)
Weekly. The single most important word about this drug.
Also: injection, pen injector
Mechanism
A folate antagonist inhibiting dihydrofolate reductase and, at the low doses used in inflammatory disease, promoting adenosine release with anti-inflammatory effect. The oncology mechanism and the rheumatology mechanism are not the same.
Indications
- Rheumatoid arthritis
- Psoriasis and psoriatic arthritis
- Crohn disease
- Ectopic pregnancy and malignancy at far higher doses
Formulations
Dosing concepts
Once weekly
For inflammatory disease it is taken ONCE A WEEK on a named day. Daily administration causes severe mucositis, marrow failure and death, and it remains one of the most reported fatal medication errors worldwide.
Folic acid
Supplementation on the other days reduces mucositis, nausea and transaminase elevation without abolishing efficacy. It is standard, not optional.
Renal impairment
Renally cleared and contraindicated at low clearance; an acute kidney injury during therapy is a medical emergency for this drug.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~60% oral at low doses, saturable
- Half-life
- 3 to 10 h at low doses
- Elimination
- renal: Renal excretion; NSAIDs, trimethoprim and probenecid reduce clearance and precipitate toxicity
- Protein binding
- ~50%
Adverse effects
- Nausea and mucositiscommonLargely preventable with folic acid.
- Myelosuppressionserious
- Hepatotoxicityserious
- PneumonitisseriousCan occur at any point; new breathlessness or dry cough warrants urgent assessment.
- TeratogenicityseriousAbsolute contraindication in pregnancy, with contraception required for both partners for a period after stopping.
- Infection riskserious
Contraindications & precautions
Contraindications
- Pregnancy and breastfeeding
- Significant renal impairment
- Chronic liver disease or significant alcohol use
- Active infection
- Pre-existing marrow suppression
Precautions
- Concurrent NSAIDs or trimethoprim
- Third-space fluid such as ascites or effusions, which prolongs exposure
- Live vaccines
Interactions
Monitoring
Full blood count, liver enzymes and creatinine
The three toxicities that are checkable · Every 2 to 4 weeks initially, then every 8 to 12 weeks
Respiratory symptoms
Pneumonitis, which no blood test predicts
That the prescription says WEEKLY, with a named day
The error that kills people
Pregnancy planning for either partner
Teratogenicity
Counselling points
- This is taken ONCE A WEEK, on the same day each week. Never daily.
- Take your folic acid on the days you are told, not on your methotrexate day.
- Report mouth ulcers, sore throat, fever, unusual bruising, or new breathlessness.
- Avoid alcohol, and tell us about any new medicine, especially anti-inflammatories and antibiotics.
- Do not become pregnant on this, and speak to us well before planning to.
Clinical pearls
- Writing the day of the week on the prescription, and having the patient say it back, is a genuine safety intervention with a documented body count behind it.
- Trimethoprim and methotrexate are both folate antagonists; the combination has caused fatal pancytopenia and is avoided outright.
- In a patient on methotrexate with new breathlessness, pneumonitis is the diagnosis to exclude before reaching for infection.
References & review
- Methotrexate product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.