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DMARD (Disease-Modifying Antirheumatic Drug) / Immunosuppressant Pregnancy: CONTRAINDICATED. Abortifacient and teratogenic. Stop 3 months before conception (both sexes).

Methotrexate (Low-dose)

Brand names: Methofar, Metoject, Maxtrex

Adult dose

Dose: 7.5–25 mg once weekly
Route: Oral or SC (Metoject pre-filled syringe)
Frequency: ONCE WEEKLY only (critical — daily dosing is fatal)
Max: 25 mg/week
RA: start 7.5–10 mg once weekly. Increase by 2.5–5 mg every 4–8 weeks to max 25 mg/week. SC route has higher bioavailability than oral (especially >15 mg/week). MUST take folic acid 5 mg once weekly (24–48 hours after methotrexate dose) to reduce side effects.

Paediatric dose

Route: SC or oral
Frequency: Once weekly
Max: 20–25 mg/m²/week
Concentration: 50 mg/m²/ml
JIA: 10–15 mg/m² once weekly (max 20–25 mg/m²). SC route preferred (better bioavailability, fewer GI effects). Folic acid 5 mg once weekly (next day after MTX) mandatory.

Dose adjustments

Renal

Avoid if eGFR <30 (accumulation and severe toxicity). Reduce dose if eGFR 30–50.

Hepatic

Avoid in significant hepatic impairment or alcohol excess (hepatotoxic).

Clinical pearls

  • ONCE WEEKLY dosing — daily dosing is a well-known FATAL prescribing error; clearly label prescription
  • Folic acid 5 mg once weekly (not on same day as MTX) reduces oral ulcers, GI effects, and hepatotoxicity
  • Report any new cough or breathlessness urgently — potential MTX pneumonitis
  • MUST advise: no live vaccines, avoid alcohol, effective contraception (3 months washout pre-conception)
  • BSR shared care monitoring protocol: FBC, LFTs, U&E at baseline then monthly (first 3–6 months) then 3-monthly

Contraindications

  • Severe renal impairment (eGFR <30)
  • Significant hepatic disease
  • Pregnancy and breastfeeding
  • Active significant infection
  • Immunodeficiency states
  • Significant alcohol use

Side effects

  • Mucositis and mouth ulcers
  • Nausea and vomiting (take at night, with food, or SC route)
  • Hepatotoxicity (fibrosis with cumulative dose — LFT monitoring)
  • Pulmonary toxicity (methotrexate pneumonitis — cough, dyspnoea — stop immediately)
  • Bone marrow suppression (megaloblastic anaemia, neutropenia, thrombocytopenia)
  • Teratogenicity (stop 3 months before conception — both male and female)

Interactions

  • NSAIDs — reduce MTX excretion (caution in high doses; low-dose NSAIDs usually acceptable in RA)
  • Co-trimoxazole/trimethoprim — antifolate — avoid combination (haematological toxicity)
  • Probenecid — increases MTX levels
  • Penicillins — reduce renal MTX excretion (avoid high-dose combination)

Monitoring

  • FBC (monthly initially then 3-monthly)
  • LFTs (monthly initially then 3-monthly)
  • U&E and creatinine
  • Chest X-ray (baseline)
  • PEFR/spirometry if respiratory symptoms

Reference: BNFc; BNF; BSR/BHPR Guidelines for MTX; NICE NG100 RA. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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