Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines. It is considered an 'important' drug as whilst it can be very effective in controlling disease the side-effects may be potentially life-threatening - careful prescribing and close monitoring is essential.

Mechanism of action

Inhibits dihydrofolate reductase


  • Inflammatory arthritis, especially rheumatoid arthritis
  • Psoriasis
  • Some chemotherapy acute lymphoblastic leukaemia

Adverse effects


  • Women should avoid pregnancy for at least 6 months after treatment has stopped
  • The BNF also advises that men using methotrexate need to use effective contraception for at least 6 months after treatment

  • Avoid prescribing trimethoprim or co-trimoxazole concurrently - increases risk of marrow aplasia
  • High-dose aspirin increases the risk of methotrexate toxicity secondary to reduced excretion


Prescribing methotrexate
  • Methotrexate is a drug with a high potential for patient harm. It is therefore important that you are familiar with guidelines relating to its use
  • Methotrexate is taken weekly, rather than daily
  • FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines recommend 'FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months'
  • Folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after methotrexate dose
  • The starting dose of methotrexate is 7.5 mg weekly (source: BNF)
  • Only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)