Adult Dosing
Levoleucovorin rescue after high-dose methotrexate therapy
- Normal methotrexate elimination
- 7.5 mg IV q6 hrs x 10 doses; start 24 hrs after methotrexate administration
- Continue until methotrexate level <0.05 micromolar; may increase to 14 doses with subsequent cycles if abnormal methotrexate elimination
- Note: Follow this regimen if methotrexate levels ~ 10 micromolar at 24 hrs, 1 micromolar at 48 hrs, and <0.2 micromolar at 72 hrs after methotrexate administration
- Delayed late methotrexate elimination
- 7.5 mg IV q6 hrs; continue until methotrexate level <0.05 micromolar
- Note: Follow this regimen if methotrexate level >0.2 micromolar at 72 hrs and >0.05 micromolar at 96 hrs after methotrexate administration
- Delayed early methotrexate elimination and/or acute renal injury
- Dose: 75 mg IV q3 hrs until methotrexate level <1 micromolar, then 7.5 mg IV q3 hrs until methotrexate levels <0.05 micromolar
- Note: Follow this regimen if methotrexate level >50 micromolar at 24 hrs, or >5 micromolar at 48 hrs OR if serum creatinine increases 100% from baseline at 24 hrs after methotrexate administration
Levoleucovorin rescue, methotrexate overdose
- Start ASAP after overdose and within 24 hrs if delayed methotrexate elimination
- Dose: 7.5 mg IV q6 hrs; continue until methotrexate level <0.01 micromolar; increase dose to 50 mg/m2 IV q3 hrs if serum creatinine increases 50% from baseline at 24 hrs or if methotrexate level >5 micromolar at 24 hrs or >0.9 micromolar at 48 hrs
Colorectal Cancer
- 100mg/m2 slow IV over a minimum of 3 min, followed by 370mg/m2 5-FU IV daily x 5 days or 10 mg/m2 followed by 425mg/m2 5-FU IV daily x 5 days
- Repeat at 4-week intervals for 2 courses, then at 4-5 week intervals until patient recovers from the toxic effects of the prior treatment course
- Increase dose of 5FU by 10% if no toxicity, and consider reducing 5-FU daily dose by 20% with moderate GI/hematologic toxicity and by 30% with severe toxicity
Pediatric Dosing
Levoleucovorin rescue after high-dose methotrexate
Child >6 yrs
- Normal methotrexate elimination
- 7.5 mg IV q6 hrs x 10 doses; Start 24 hrs after methotrexate administration
- Continue until methotrexate level <0.05 micromolar; may incr. to 14 doses w/ subsequent cycles if abnormal methotrexate elimination
- Note: Follow this regimen if methotrexate levels ~ 10 micromolar at 24 hrs, 1 micromolar at 48 hrs, and <0.2 micromolar at 72 hrs after methotrexate administration
- Delayed late methotrexate elimination
- 7.5 mg IV q6 hrs; continue until methotrexate level <0.05 micromolar
- Note: Follow this regimen if methotrexate level >0.2 micromolar at 72 hrs and >0.05 micromolar at 96 hrs after methotrexate administration
- Delayed early methotrexate elimination and/or acute renal injury
- Dose: 75 mg IV q3 hrs until methotrexate level <1 micromolar, then 7.5 mg IV q3 hrs until methotrexate levels <0.05 micromolar
- Note: Follow this regimen if methotrexate level >50 micromolar at 24 hrs, or >5 micromolar at 48 hrs OR if serum creatinine increases 100% from baseline at 24 hrs after methotrexate administration
Levoleucovorin rescue, methotrexate overdose
Child >6 yrs
- Start ASAP after overdose and within 24 hrs if delayed methotrexate elimination
- Dose: 7.5 mg IV q6 hrs; continue until methotrexate level <0.01 micromolar; increase dose to 50 mg/m2 IV q3 hrs if serum creatinine increases 50% from baseline at 24 hrs or if methotrexate level >5 micromolar at 24 hrs or >0.9 micromolar at 48 hrs
- Do not administer intrathecally
- Toxicity of fluorouracil is enhanced by levoleucovorin. Deaths due to severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly <i>d,l</i>-leucovorin and 5-fluorouracil
- Due to calcium content, do not administer I.V. solutions at a rate >160 mg levoleucovorin/minute
- Concomitant use of <i>d,l</i>-leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection has been associated with increased rates of treatment failure and morbidity
- Not for treating pernicious anemia and megaloblastic anemia
- Do not co-administer with other agents in the same admixture (risk of precipitation)
- Monitor serum creatinine and methotrexate levels q24 hrs
- Delayed early methotrexate elimination may cause reversible renal failure; provide hydration, alkalinize urine with sodium bicarbonate, closely monitor fluid and electrolytes until serum methotrexate <0.05 micromolar and renal failure resolves
Cautions: Use cautiously in
- Vitamin B-12 deficiency
- Pernicious anemia
- Megaloblastic anemia; vitamin B-12 deficient
Pregnancy Category:C
Breastfeeding: Safety unknown. Manufacturer advises caution.
