How do you calculate the methotrexate (methotrexate) dose per meter square (m^2)?

Calculating Methotrexate Dose Per Meter Square

To calculate methotrexate dose per m², first determine the patient's body surface area (BSA) using the Mosteller formula: BSA (m²) = √[(height in cm × weight in kg) / 3600], then multiply the BSA by the prescribed dose per m² for the specific indication. 1

Body Surface Area Calculation

The Mosteller formula is the most widely accepted method for calculating BSA in clinical practice 1:

• BSA (m²) = √[(height in cm × weight in kg) / 3600] 1
• Alternative validated calculators (DuBois, Haycock) may be used, though Mosteller is preferred 1
• BSA is difficult to measure directly but can be reliably estimated using these weight and height-based formulae 2

Dose Calculation Formula

Once BSA is calculated, the methotrexate dose is determined by:

• Dose (mg) = Prescribed dose per m² × Patient's BSA (m²) 1
• Round to the nearest available tablet strength (typically 2.5 mg increments) 1
• For oral administration, 0.1 mL of 25 mg/mL injection solution equals a 2.5 mg oral tablet if conversion is needed 3, 1

Standard Dosing Ranges by Indication

Juvenile Idiopathic Arthritis (Polyarticular)

• Starting dose: 10 mg/m² BSA per week 3, 4
• Low to moderate disease activity: 10-15 mg/m² BSA per week 3
• Maximum recommended: 15 mg/m² BSA per week (no additional benefit above this dose) 3
• Doses above 15 mg/m² BSA per week should use parenteral (subcutaneous) route rather than oral 3
• Absolute maximum: 25 mg per week regardless of BSA calculation 1, 4

Pediatric Crohn's Disease

• 15 mg/m² BSA once weekly, maximum 25 mg 1

Psoriasis and Atopic Dermatitis (Adults)

• Typical weekly dosing: 7.5 to 25 mg per week 3
• BSA-based dosing is less commonly used for these indications; fixed weekly doses are standard 3, 1
• Dosing should be adjusted to achieve adequate disease control while minimizing cumulative dose 3

Osteosarcoma (High-Dose Regimen)

• Starting dose: 12 g/m² IV as 4-hour infusion 4
• May escalate to 15 g/m² if peak serum concentration does not reach 1,000 micromolar 4
• Requires leucovorin rescue starting 24 hours after methotrexate infusion 4

Practical Calculation Example

For a child with polyarticular JIA:

• Height: 140 cm, Weight: 35 kg
• BSA = √[(140 × 35) / 3600] = √[4900 / 3600] = √1.36 = 1.17 m²
• Prescribed dose: 10 mg/m² per week
• Calculated dose: 10 × 1.17 = 11.7 mg, round to 12.5 mg (nearest tablet strength) 1

Important Dosing Considerations

Route of Administration

• Parenteral (subcutaneous or intramuscular) administration has higher bioavailability than oral dosing 3, 1
• Oral absorption is dose-dependent and saturable; doses above 15-40 mg/m² have significantly reduced absorption 3, 4
• For doses ≥15 mg/m² BSA per week, subcutaneous route is preferred to ensure adequate absorption 3

Renal Impairment

• Reduce dose by 50% for creatinine clearance 20-50 mL/min 1
• Methotrexate is contraindicated if eGFR <30 mL/min 5
• Renal function must be documented before each treatment course for high-dose regimens 4

Test Dose Protocol

• Consider a test dose of 2.5 or 5 mg with CBC evaluation 5-6 days later 3
• Mandatory in patients with decreased glomerular filtration rate or significant risk factors for hematologic toxicity 3
• Does not guarantee prevention of myelosuppression but identifies extreme sensitivity 3

Pediatric Considerations

• For children with JIA, weight-based dosing (maximum 1 mg/kg, not exceeding 25 mg/week) may be easier to calculate than BSA-based dosing 1
• Children receiving 20-30 mg/m²/week may have better absorption and fewer GI side effects with intramuscular or subcutaneous administration 4
• Significant interindividual variability exists in oral absorption in pediatric patients (23% to 95% bioavailability) 4

Mandatory Safety Requirements

Folate Supplementation

• Folic acid 1-5 mg daily on non-methotrexate days is mandatory to reduce toxicity 3, 1
• Administer daily except the day of methotrexate 3
• May increase dose if bone marrow toxicity or GI side effects develop despite supplementation 3

Monitoring Schedule

• Baseline: CBC, liver function tests, renal function (creatinine, creatinine clearance) 3
• First 6 months: Monthly liver function tests 3
• Ongoing: Every 3-6 months for liver function tests assuming no abnormalities 3
• More frequent monitoring with dosage increases (pancytopenia may occur 4-6 weeks after dose escalation) 3

High-Dose Methotrexate Safety Guidelines

For doses ≥500 mg/m² (high-dose regimens):

• Delay administration if WBC <1500/μL, neutrophils <200/μL, platelets <75,000/μL, bilirubin >1.2 mg/dL, or SGPT >450 U 4
• Serum creatinine must be normal and creatinine clearance >60 mL/min before each course 4
• Hydration: 1,000 mL/m² IV over 6 hours before infusion, continue at 125 mL/m²/hr during and for 2 days after 4
• Urinary alkalinization to maintain pH >7.0 throughout treatment 4
• Monitor serum methotrexate levels 24 hours after starting and daily until <0.05 micromolar 4

Common Pitfalls to Avoid

• Do not exceed 20 mg/week in adults without careful consideration - significant increase in serious toxic reactions above this dose 4
• Do not use BSA-calculated doses above 25 mg/week as absolute maximum regardless of calculated BSA 3, 1, 4
• Do not rely on oral administration for doses ≥15 mg/m² due to saturable absorption 3, 4
• Do not forget the test dose in high-risk patients (renal impairment, elderly, drug interactions) 3
• Do not confuse daily dosing with weekly dosing - methotrexate for RA/psoriasis/JIA is weekly, not daily 3, 6