What is the dosing regimen for methotrexate?

Methotrexate Dosing Regimen

Methotrexate should be dosed at 7.5-25 mg once weekly for most indications, with dose individualization based on disease severity, patient characteristics, and monitoring of adverse effects. 1

Initial Dosing

• For psoriasis and rheumatoid arthritis, start with 7.5-15 mg weekly as a single dose or divided into 3 doses over 24 hours 1
• A test dose of 2.5-5 mg is recommended before starting full therapy, especially in patients with impaired kidney function 1
• The initial dose should not exceed 0.2 mg/kg body weight in any circumstance 1
• For patients over 70 years or with renal impairment, consider starting at lower doses (2.5-5 mg weekly) 1

Dose Escalation

• If laboratory results are normal after initial dose, regular maintenance treatment may begin one week later 1
• Doses can be increased gradually by 2.5-5 mg every 2-4 weeks if needed for disease control 1
• Maximum recommended dose is typically 25-30 mg weekly 1
• Allow 4 weeks after dose adjustments to assess clinical response before further changes 1

Route of Administration

• Oral administration is most common and preferred by most patients 1
• Subcutaneous or intramuscular administration may be considered if:
  • Oral therapy is not tolerated (especially for GI side effects) 1
  • Higher bioavailability is needed for better efficacy 1
  • Patient has inadequate response to oral therapy 1

Monitoring Schedule

• Before starting: Complete blood count, liver function tests, serum creatinine 1
• First month: Weekly monitoring of CBC, liver function, and renal function 1
• Maintenance: Every 1-2 months for stable patients 1
• More frequent monitoring for patients with risk factors for toxicity 1

Folate Supplementation

• Folic acid supplementation (1-5 mg daily) is strongly recommended except on the day of methotrexate administration 1
• Folate reduces the incidence of gastrointestinal side effects, hepatic abnormalities, and potentially hematologic toxicity 1
• Folinic acid (leucovorin) is an alternative but more expensive option with no proven advantage over folic acid 1

Common Pitfalls to Avoid

• Never administer methotrexate daily - this increases toxicity significantly 2
• Avoid prescribing to patients with significant hepatic damage, severe anemia, leukopenia, or thrombocytopenia 1
• Methotrexate is contraindicated during pregnancy, breastfeeding, and for men wishing to father children 1
• Avoid concomitant use of drugs that interact with methotrexate: alcohol, salicylates, NSAIDs, co-trimoxazole, trimethoprim, probenecid, phenytoin, retinoids, pyrimethamine, and frusemide 1
• Ensure patients understand the weekly dosing schedule to prevent potentially fatal dosing errors 1, 2

Response Evaluation

• Clinical response to methotrexate typically takes 4-8 weeks to manifest 1
• For psoriasis, expect a response within 2 weeks of starting therapy 1
• For rheumatoid arthritis, response may take up to 12 weeks 3
• If no adequate response is achieved after 12-16 weeks at maximum tolerated dose, consider alternative therapy 1