Generic Name: levoleucovorin calcium
Dosage Form: injection, powder, lyophilized, for solution
Indications and Usage for Fusilev
•Fusilev® is a folate analog.
•Fusilev rescue is indicated after high-dose methotrexate therapy in osteosarcoma.
•Fusilev is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.
•Fusilev is indicated for use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer.
Limitations of Use
•Fusilev is not approved for pernicious anemia and megaloblastic anemias secondary to the lack of vitamin B12. Improper use may cause a hematologic remission while neurologic manifestations continue to progress.
Fusilev Dosage and Administration
Administration Guidelines
Fusilev is dosed at one-half the usual dose of racemic d,l-leucovorin.
Fusilev is indicated for intravenous administration only. Do not administer intrathecally.
Co-administration of Fusilev with other agents
Due to the risk of precipitation, do not co-administer Fusilev with other agents in the same admixture.
Fusilev Rescue After High-Dose Methotrexate Therapy
The recommendations for Fusilev rescue are based on a methotrexate dose of 12 grams/m2 administered by intravenous infusion over 4 hours (see methotrexate package insert for full prescribing information). Fusilev rescue at a dose of 7.5 mg (approximately 5 mg/m2) every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion.
Serum creatinine and methotrexate levels should be determined at least once daily. Fusilev administration, hydration, and urinary alkalinization (pH of 7.0 or greater) should be continued until the methotrexate level is below 5 x 10-8 M (0.05 micromolar). The Fusilev dose should be adjusted or rescue extended based on the following guidelines.
Table 1 Guidelines for Fusilev Dosage and Administration Clinical Situation Laboratory Findings Fusilev Dosage and Duration
Normal Methotrexate Elimination Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours 7.5 mg IV q 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion).
Delayed Late Methotrexate Elimination Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration. Continue 7.5 mg IV q 6 hours, until methotrexate level is less than 0.05 micromolar.
Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more). 75 mg IV q 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg IV q 3 hours until methotrexate level is less than 0.05 micromolar.
Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate Fusilev therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status,