25/04/2026
# # Methotrexate Administration in Rheumatoid Arthritis
**Route of Administration:**
- **Oral** or **parenteral (subcutaneous/intramuscular)**
- Subcutaneous route may be substituted if oral therapy is inadequate
**Dosing:**
- **Starting dose:** 15 mg once weekly
- **Maximum dose:** 25 mg weekly (in adults)
- Dose is escalated gradually based on response and tolerability
**Essential Co-prescription:**
- **Folic acid 5 mg weekly** should be taken the day after methotrexate to reduce adverse effects without impairing efficacy
**Timing Considerations:**
- **Onset of benefit:** 2-8 weeks after starting therapy
- **Full effectiveness:** May take up to 3 months
- Continue for at least 3 months before concluding treatment is ineffective
**Key Monitoring Points:**
*Common adverse effects (typically 1-2 days post-dose):*
- Nausea, vomiting, malaise
- Oral ulcers
- Hepatotoxicity
- Cytopenias
*Serious adverse effects:*
- Pneumonitis (rare but can occur anytime) - patients should stop therapy immediately and seek medical advice if new respiratory symptoms develop
**Important Contraindications:**
- Chronic liver disease
- Excess alcohol use (>2 drinks/day for males, >1 drink/day for females)
- Pregnancy - must use robust contraception and stop methotrexate 3 months before planning pregnancy
**Drug Interactions:**
- Avoid sulphonamides
- Avoid excess alcohol (enhances hepatotoxicity)
**Treatment Strategy:**
Methotrexate is the first-line DMARD of choice for most RA patients. If inadequate response occurs, options include:
- Adding other conventional DMARDs (triple therapy with hydroxychloroquine and sulfasalazine is common)
- Switching to subcutaneous administration
- Progressing to biologic DMARDs
Methotrexate remains the most effective single DMARD available, with sustained efficacy demonstrated for up to 15 years in some patients.
