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-fl fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Leucovorin should not be mixed in the same infusion as 5-fl fluorouracil because a precipitate may form.

•Advanced Colorectal Cancer: Either of the following two regimens is recommended: Leucovorin is administered at 200 mg/m 2 by slow intravenous injection over a minimum of 3 minutes, followed by 5-fl fluorouracil at 370 mg/m 2 by intravenous injection.
•Leucovorin is administered at 20 mg/m 2 by intravenous injection followed by 5-fl uorouracil at 425 mg/m 2 by intravenous injection. 5-Fluorouracil and leucovorin should be administered separately to avoid the formation of a precipitate See package insert for complete information.

Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following the administration of both oral and parenteral leucovorin. No other adverse reactions have been attributed to the use of leucovorin per see. The following table summarizes significant adverse events occurring in 316 patients treated with the leucovorin/5-fl uorouracil combinations compared against 70 patients treated with 5-fl uorouracil alone for advanced colorectal carcinoma. These data are taken from the Mayo/NCCTG large multicenter prospective trial evaluating the efficacy and safety of the combination regimen.

Leucovorin is an improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B12. A hematologic remission may occur while neurologic manifestations continue to progress.

Parenteral administration is preferable to oral dosing if there is a possibility that the patient may vomit and not absorb the leucovorin. Leucovorin has no effect on non-hematologic toxicities of methotrexate such as the nephrotoxicity resulting from drug and/ or metabolite precipitation in the kidney. See package insert for complete information.