Leucovorin Rescue After High-Dose Methotrexate

Essential Supportive Measures

The American College of Physicians recommends aggressive IV hydration at 3 L/day or 125 ml/m²/hr, and urinary alkalinization to maintain urine pH ≥7.0 using sodium bicarbonate, to be continued until methotrexate level <5 × 10⁻⁸ M (0.05 micromolar) 1
Monitoring of serum creatinine and methotrexate levels should be done at least once daily, with adjustments to leucovorin dosing based on elevated serum creatinine 1

For lower-dose methotrexate (50 mg IM every 48 hours × 4 doses) in low-risk gestational trophoblastic neoplasia, the National Comprehensive Cancer Network recommends leucovorin 15 mg orally 30 hours after each methotrexate injection 2
For methotrexate 300 mg/m² IV over 12 hours in high-risk gestational trophoblastic neoplasia (EMA/CO Regimen), the European Society for Medical Oncology recommends leucovorin 15 mg IV or orally every 12 hours for 4 doses, starting 24 hours after commencing methotrexate infusion 2
For intermediate-dose methotrexate (1 g/m² over 24 hours) in acute lymphoblastic leukemia (Limited Resources), the American Society of Clinical Oncology recommends leucovorin 10 mg/m² starting at 42 hours, repeated every 6 hours for 3 doses, with increase in leucovorin rescue based on elevated serum creatinine 5

For inadvertent methotrexate overdose or severe toxicity, the American Association of Clinical Toxicology recommends hospital admission for monitoring, activated charcoal if ≥1 mg/kg ingested within 1 hour, G-CSF (filgrastim 5 mcg/kg/day subcutaneously) for toxic bone marrow suppression, and sepsis monitoring due to high mortality risk 1