Methotrexate

How it works

It inhibits dihydrofolate reductase and other folate-dependent enzymes; at low weekly doses its anti-inflammatory action is attributed largely to adenosine-mediated immunomodulation.

Prescribing in practice

• It is dosed ONCE WEEKLY and inadvertent daily dosing causes severe, potentially fatal toxicity, so the weekly schedule must be reinforced at every step.
• Bone marrow suppression, hepatotoxicity and pneumonitis are key risks requiring regular monitoring and prompt response to symptoms.
• It is contraindicated in pregnancy and significant renal or hepatic impairment, and interacts dangerously with trimethoprim and other antifolates.

Monitoring

Monitor full blood count, renal function and liver function regularly per shared-care protocols, with folic acid co-prescribed to reduce toxicity as advised in the SPC.

Counselling the patient

• Take it only once a week on the same chosen day and never daily.
• Report sore throat, fever, breathlessness, persistent cough or unusual bruising urgently.
• Avoid pregnancy, limit alcohol, and take folic acid as prescribed.

Evidence & guidelines

Decades of randomised trial and registry evidence establish methotrexate as first-line therapy and the backbone of combination DMARD treatment in rheumatoid arthritis.