Leucovorin

Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. In contrast, leucovorin can enhance the therapeutic and toxic effects of fluoropyrimidines used in cancer therapy, such as 5-fluorouracil. Concurrent administration of leucovorin does not appear to alter the plasma pharmacokinetics of 5-fluorouracil. 5-Fluorouracil is metabolized to fluorodeoxyuridylic acid, which binds to and inhibits the enzyme thymidylate synthase (an enzyme important in DNA repair and replication).

Advanced Colorectal Cancer

Either of the following two regimens is recommended:

1. Leucovorin is administered at 200 mg/m2 by slow intravenous injection over a minimum of 3 minutes, followed by 5-fluorouracil at 370 mg/m2 by intravenous injection.

2. Leucovorin is administered at 20 mg/m2 by intravenous injection followed by 5-fluorouracil at 425 mg/m2 by intravenous injection.

Leucovorin Rescue after High-Dose Methotrexate Therapy

The recommendations for leucovorin rescue are based on a methotrexate dose of 12 to 15 grams/m2  administered by intravenous infusion over 4 hours (see methotrexate package insert for full prescribing information). Leucovorin rescue at a dose of 15 mg (approximately 10 mg/m2) every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. In the presence of gastrointestinal toxicity, nausea or vomiting, leucovorin should be administered parenterally. Do not administer leucovorin intrathecally.

Leucovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma.

Leucovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of  inadvertent overdosages of folic acid antagonists.

Leucovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible.

Leucovorin is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

Leucovorin calcium Injection is available as 2 ml & 5 ml vial containing 15 mg & 50 mg of leucovorin respectively.

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory