Levoleucovorin Rescue Following High-Dose Methotrexate—Based on a Methotrexate Dose of 12 g/m2 IV Over 4 hr and Concurrent with Hydration and Maintenance of Urine pH 7.0

• IV (Adults and Children ≥6 yr): Normal methotrexate elimination: 7.5 mg (5 mg/m²) every 6 hr for 10 doses starting 24 hr after the start of the methotrexate infusion; Delayed late methotrexate elimination: 7.5 mg (5 mg/m²) every 6 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level <5 × 10^–8 (0.05 micromolar); Delayed early methotrexate elimination and/or evidence of acute renal injury: 75 mg (5 mg/m²) every 3 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level is <1 micromolar; then 7.5 mg every 3 hr until 0.05 micromolar).

Levoleucovorin Rescue Following Inadvertent Overdosage of Methotrexate

• IV (Adults and Children ≥6 yr): 7.5 mg (approximately 5 mg/m²) every 6 hr until serum methotrexate level <10⁻⁸ M. Determine serum creatinine and methotrexate levels at 24-hr intervals. If 24-hr serum creatinine has ↑ 50% over baseline or 24-hr methotrexate level is >5 × 10⁻⁶ M or 48-hr level is >9 × 10⁻⁷ M, ↑ dose to 50 mg/m² IV every 3 hr until methotrexate level is <10⁻⁸ M. Maintain hydration and urinary alkalinization (pH ≥7.0). Initiate as soon as possible and within 24 hr of methotrexate when there is delayed excretion; as time interval increases, effectiveness ↓.

Palliative Treatment of Advanced Metastatic Colorectal Cancer

• IV (Adults ): 100 mg/m² followed by 5-fluorouracil 370 mg/m²; regimen should be given daily for 5 days; repeat regimen every 4 wk for 2 courses (may then repeat course every 4–5 wk if patient tolerates) or levoleucovorin 10 mg/m² followed by 5-fluorouracil 425 mg/m²; regimen should be given daily for 5 days; repeat regimen every 4 wk for 2 courses (may then repeat course every 4–5 wk if patient tolerates).