levoleucovorin [IV]

Adult Dosing

Levoleucovorin rescue after high-dose methotrexate therapy

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

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

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

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

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

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

[Outline]

Indications ⬆ ⬇

In osteosarcoma, to reduce toxicity of high-dose methotrexate therapy
To diminish toxicity and counteract effects of impaired methotrexate elimination and of inadvertent overdose of folic acid antagonists
Treatment of patients with advanced metastatic colorectal cancer in combination chemotherapy with 5-fluorouracil
Note: Not approved for pernicious anemia and megaloblastic anemias secondary to vitamin B₁₂ deficiency

Contraindications ⬆ ⬇

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Hepatic Dose Adjustment

Warnings/Precautions ⬆ ⬇

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

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:C

Breastfeeding: Safety unknown. Manufacturer advises caution.

Adverse Reactions ⬆ ⬇

Clinical Pharmacology ⬆ ⬇

Antidote; counteract therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase
IV administration results in complete bioavailability
Extensively converted to tetrahydrofolic derivatives
Metabolized in the GUT and liver; CYP450: Unknown
Renally excreted
Half-Life: 6.8 hrs

Brands and Availability ⬆ ⬇