How is the dose of methotrexate (MTX) per meter square calculated?

Calculating Methotrexate Dose Per Meter Square

Methotrexate dosing based on body surface area (BSA) is calculated using the formula: Dose (mg) = Prescribed dose per m² × Patient's BSA (m²), where BSA is typically calculated using the Mosteller formula or similar validated equations.

Body Surface Area Calculation

• BSA is calculated using standard formulas, most commonly the Mosteller formula: BSA (m²) = √[(height in cm × weight in kg) / 3600] 1
• Alternative validated BSA calculators (DuBois, Haycock) may also be used, though the Mosteller formula is most widely accepted in clinical practice 1

Standard Dosing Ranges by Indication

Pediatric Inflammatory Skin Disease

• Weight-based dosing may be easier to calculate than BSA-based dosing and has been safely used in many studies, though both approaches are acceptable 1
• When using BSA dosing, the maximum dose is 1 mg/kg (not exceeding 25 mg/week) regardless of calculated BSA 1

Pediatric Crohn's Disease

• Methotrexate should be prescribed at 15 mg/m² once weekly, with a maximum dose of 25 mg 1
• After sustained remission with normal inflammatory markers, attempt dose reduction 1

Rheumatoid Arthritis (Adult and Pediatric)

• Polyarticular-course juvenile rheumatoid arthritis: recommended starting dose is 10 mg/m² given once weekly 2
• Dosages may be adjusted gradually to achieve optimal response 2
• Limited experience shows significant increase in serious toxic reactions at doses greater than 20 mg/week in adults 2
• Children receiving 20-30 mg/m²/week (0.65-1 mg/kg/week) may have better absorption with intramuscular or subcutaneous administration 2

Psoriasis

• Typical dosing ranges from 7.5 mg to 25 mg weekly, though BSA-based dosing is less commonly used for this indication 1
• The recommended starting dose schedule is 10-25 mg per week until adequate response is achieved, with 30 mg/week not ordinarily exceeded 2

Practical Calculation Example

For a patient prescribed 15 mg/m² weekly:

1. Calculate patient's BSA using height and weight
2. Multiply BSA by 15 mg/m²
3. Round to nearest available tablet strength (typically 2.5 mg increments)
4. Do not exceed 25 mg total weekly dose regardless of calculated amount 1, 2

Important Clinical Considerations

Route of Administration

• Parenteral (subcutaneous or intramuscular) administration likely results in higher bioavailability and may increase efficacy compared to oral dosing 1
• Children with higher BSA-based doses (20-30 mg/m²/week) may benefit from parenteral administration due to better absorption 2
• 0.1 mL of 25 mg/mL injection solution is equivalent to a 2.5 mg oral tablet, making conversion straightforward 1

Dosing Schedule

• Methotrexate is usually given as a single weekly dose 1
• Divided dosing (3 doses given every 12 hours over 24 hours) may improve gastrointestinal tolerability in some patients 1

Renal Impairment Adjustments

• Patients with renal impairment may need lower doses and could be commenced on 2.5-5 mg weekly 1
• Dose reduction (50% reduction) is recommended for creatinine clearance 20-50 mL/min, and methotrexate is contraindicated if creatinine clearance is <20 mL/min 3, 4

Test Dosing

• Test doses are not necessary for pediatric patients starting low-dose methotrexate for inflammatory skin disease 1
• Some adult physicians prefer starting with a test dose of 2.5-5 mg, followed by complete blood count 5-7 days later, though this is optional 1

Maximum Doses

• The absolute maximum weekly dose across all indications is 25-30 mg, regardless of BSA calculation 1, 2
• For high-dose methotrexate in oncology (defined as ≥500 mg/m²), different protocols and leucovorin rescue are required 4, 5

Folic Acid Supplementation

• Folic acid supplementation (1-5 mg daily on non-methotrexate days) is mandatory to reduce toxicity 1, 6, 3