Leucovorin

Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than the abnormalities described in Table 2 . These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy.

Leucovorin calcium for injection dosages are not adjusted for toxicity. Leucovorin Rescue After High-Dose Methotrexate Therapy The recommendations for leucovorin rescue are based on a methotrexate dose of 12 to 15 grams/m 2 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/m 2 ) 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 calcium for injection should be administered parenterally. Do not administer leucovorin calcium for injection intrathecally.

Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate solution should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater. Megaloblastic Anemia Due to Folic Acid Deficiency Up to 1 mg daily. There is no evidence that doses greater than 1 mg/day have greater efficacy than those of 1 mg; additionally, loss of folate in urine becomes roughly logarithmic as the amount administered exceeds 1 mg.

Each 500 mg vial of leucovorin calcium for injection when reconstituted with 50 mL of sterile diluent yields a leucovorin concentration of 10 mg per mL. Leucovorin calcium for injection contains no preservative. Reconstitute with Bacteriostatic Water for Injection, USP, which contains benzyl alcohol, or with Sterile Water for Injection, USP.

When reconstituted with Bacteriostatic Water for Injection, USP, the resulting solution must be used within 7 days. If the product is reconstituted with Sterile Water for Injection, USP, it must be used immediately. Because of the benzyl alcohol contained in Bacteriostatic Water for Injection, USP, when doses greater than 10 mg/m 2 are administered, leucovorin calcium for injection should be reconstituted with Sterile Water for Injection, USP, and used immediately (see WARNINGS ).

Because of the calcium content of the leucovorin calcium for injection solution, no more than 160 mg of leucovorin calcium for injection should be injected intravenously per minute (16 mL of a 10 mg per mL, or 8 mL of a 20 mg per mL solution per minute). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Leucovorin calcium for injection should not be mixed in the same infusion as 5-fluorouracil, since this may lead to the formation of a precipitate.