Starting Dose of Methotrexate for Psoriasis
The recommended starting dose of methotrexate for psoriasis is either a test dose of 2.5-5 mg followed by a therapeutic dose of 7.5-15 mg weekly, or starting directly at 15 mg weekly in low-risk patients, with the option to use higher initial doses (up to 25 mg weekly) in severe disease requiring faster control. 1, 2
Initial Dosing Strategy
The 2020 Joint American Academy of Dermatology-National Psoriasis Foundation guidelines provide two acceptable approaches 1:
Option 1: Test Dose Approach (Preferred for High-Risk Patients)
- Start with a test dose of 2.5-5 mg, followed by a complete blood count 5-7 days later to assess individual susceptibility to bone marrow suppression 1, 2
- This approach is mandatory for patients with:
- If the test dose is tolerated (normal CBC), proceed to therapeutic dosing one week later 1
Option 2: Direct Therapeutic Dosing (For Low-Risk Patients)
- Begin at 15 mg weekly without a test dose in patients without risk factors 1, 2
- This approach is reasonable when there are no concerns about drug interactions, renal function, or other comorbidities 1
- The FDA label supports starting doses of 10-25 mg per week for psoriasis 3
Dosing Range and Administration
The typical therapeutic range is 7.5-25 mg weekly, administered as a single dose or divided into 3 doses over 24 hours 1:
- Lower starting doses (7.5-10 mg weekly): Slower acting but with fewer severe adverse effects 1, 4
- Higher starting doses (15-25 mg weekly): Faster therapeutic response, particularly useful for severe or unstable psoriasis (pustular, erythrodermic) 1, 4
- Maximum dose should not exceed 0.2 mg/kg body weight for the initial dose 1
Route of Administration
- Oral administration is preferred initially 1
- Subcutaneous or intramuscular routes may be considered if gastrointestinal side effects are problematic or higher bioavailability is needed 1, 2, 5
Critical Safety Requirements
Mandatory Folic Acid Supplementation
- Prescribe folic acid 1-5 mg daily on all days EXCEPT the day methotrexate is taken 1, 2
- This reduces hepatic abnormalities, gastrointestinal side effects, and potentially hematologic toxicity 1
Baseline Laboratory Monitoring
Before starting methotrexate, obtain 1, 2:
- Complete blood count (CBC)
- Liver function tests (AST, ALT)
- Serum creatinine and creatinine clearance
- Hepatitis B and C screening
Contraindications to Verify
- Pregnancy and breastfeeding (absolute contraindication) 1, 3
- Men wishing to father children (causes spermal abnormalities) 1
- Severe anemia, leukopenia, or thrombocytopenia 1, 3
- Significant hepatic damage 1
Dose Escalation Strategy
- Increase by 2.5-5 mg every 2-4 weeks if disease control is inadequate 2
- Allow at least 4 weeks after dose adjustments before making further changes, as clinical response takes time 1, 2
- Maximum dose typically 25-30 mg weekly (do not ordinarily exceed 30 mg/week) 2, 3
Common Pitfalls to Avoid
Daily vs. Weekly Dosing Confusion
- Methotrexate must be given WEEKLY, not daily 1, 6
- Daily dosing (2.5 mg daily for 6 days) is inferior to weekly dosing and causes more liver enzyme elevations 1, 6
- This is a critical safety issue—ensure patients understand the weekly schedule 1
Drug Interactions
Avoid or use extreme caution with 1:
- Alcohol (increases hepatotoxicity)
- NSAIDs (increase methotrexate toxicity)
- Salicylates
- Trimethoprim/co-trimoxazole
- Probenecid
Monitoring After Initiation
- CBC and liver function tests 5-7 days after test dose (if used) 1, 2
- Monthly monitoring for first 6 months, then every 3-6 months 5
- Weekly monitoring initially if starting without test dose 1
Special Populations
Elderly Patients (>70 years)
- Start with lower doses (2.5-5 mg weekly) and use test dose approach 1
- Maximum dose should not exceed 0.2 mg/kg body weight 1