Yes

Antidote; Vitamin, Water Soluble

Antidote for folic acid antagonists (methotrexate [>100 mg/m²], trimethoprim, pyrimethamine); treatment of megaloblastic anemias when folate is deficient as in infancy, sprue, pregnancy, and nutritional deficiency when oral folate therapy is not possible; in combination with fluorouracil in the treatment of malignancy

C

Pernicious anemia or vitamin B₁₂ deficient megaloblastic anemias; should NOT be administered Intrathecally/Intraventricularly

Use with caution in patients with a history of hypersensitivity

<1%: Rash, pruritus, erythema, urticaria, thrombocytosis, wheezing, anaphylactoid reactions

Increased toxicity of fluorouracil

Leucovorin injection should be stored at room temperature and protected from light

Reconstituted solution is stated to be chemically stable for 7 days; reconstitutions with bacteriostatic water for injection, U.S.P., must be used within 7 days. Doses >10 mg/m² must be prepared using leucovorin reconstituted with sterile water for injection, U.S.P., and used immediately.

Stability of parenteral admixture at room temperature (25°C): 24 hours

Stability of parenteral admixture at refrigeration temperature (4°C): 4 days

Standard diluent: 50-100 mg/50 mL D₅W

Minimum volume: 50 mL D₅W

Concentrations of >2 mg/mL of leucovorin and >25 mg/mL of fluorouracil are incompatible (precipitation occurs)

A reduced form of folic acid, but does not require a reduction reaction by an enzyme for activation, allows for purine and thymidine synthesis, a necessity for normal erythropoiesis; leucovorin supplies the necessary cofactor blocked by MTX, enters the cells via the same active transport system as MTX

Onset of activity: Oral: Within 30 minutes; rapid, well absorbed but decreases at doses >25 mg; I.V.: Within 5 minutes

Absorption: Oral, I.M.: Rapid

Metabolism: Rapidly converted to (5MTHF) 5-methyl-tetrahydrofolate (active) in the intestinal mucosa and by the liver

Half-life: Leucovorin: 15 minutes; 5MTHF: 33-35 minutes

Elimination: Primarily in urine (80% to 90%) with small losses appearing in feces (5% to 8%)

Children and Adults:

Folate-deficient megaloblastic anemia: I.M.: 1 mg/day

Megaloblastic anemia secondary to congenital deficiency of dihydrofolate reductase: I.M.: 3-6 mg/day

Rescue dose (rescue therapy should start within 24 hours of MTX therapy): I.V.: 10 mg/m² to start, then 10 mg/m² every 6 hours orally for 72 hours until serum MTX concentration is <10^-8 molar; if serum creatinine 24 hours after methotrexate is elevated 50% or more above the pre-MTX serum creatinine or the serum MTX concentration is >5 x 10^-6 molar (see graph), increase dose to 100 mg/m²/dose (preservative-free) every 3 hours until serum methotrexate level is <1 x 10^-8 molar

Investigational: Post I.T. methotrexate: Oral, I.V.: 12 mg/m² as a single dose; post high-dose methotrexate: 100-1000 mg/m²/dose until the serum methotrexate level is less than 1 x 10^-7 molar

The drug should be given parenterally instead of orally in patients with GI toxicity, nausea, vomiting, and when individual doses are >25 mg

Plasma MTX concentration as a therapeutic guide to high-dose MTX therapy with leucovorin factor rescue

Each dose of leucovorin is increased if the plasma MTX concentration is excessively high (see graph)

With 4- to 6-hour high-dose MTX infusions, plasma drug values in excess of 5 x 10^-5 and 10^-6 molar at 24 and 48 hours after starting the infusion, respectively, are often predictive of delayed MTX clearance; see graph.

None reported

None reported

No information available to require special precautions

No effects or complications reported

Take as directed, at evenly spaced intervals around-the-clock. Maintain hydration (2-3 L of water/day while taking for rescue therapy). For folic acid deficiency, eat foods high in folic acid (eg, meat proteins, bran, dried beans, asparagus, green leafy vegetables). Report respiratory difficulty, lethargy, or rash or itching. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Parenteral: Reconstitute 50 mg or 100 mg powder for injection vials with 5-10 mL concentration (350 mg vial requires 17 mL diluent resulting in 20 mg/mL); infuse at a maximum rate of 160 mg/minute

Injection, as calcium: 3 mg/mL (1 mL)

Powder for injection, as calcium: 25 mg, 50 mg, 100 mg, 350 mg

Powder for oral solution, as calcium: 1 mg/mL (60 mL)

Tablet, as calcium: 5 mg, 10 mg, 15 mg, 25 mg

Bleyer WA, "New Vistas for Leucovorin in Cancer Chemotherapy," Cancer, 1989, 63(6 Suppl):995-1007.

Hansen RM, "Systemic Therapy in Metastatic Colorectal Cancer," Arch Intern Med, 1990, 150(11):2265-9.

Jacobsen D and McMartin KE, "Methanol and Ethylene Glycol Poisonings. Mechanism of Toxicity, Clinical Course, Diagnosis and Treatment," Med Toxicol, 1986, 1(5):309-34.

Trissel LA, Martinez JF, and Xu QA, "Incompatibility of Fluorouracil With Leucovorin Calcium or Levoleucovorin Calcium," Am J Health Syst Pharm, 1995, 52(7):710-5.