Leucovorin (Leucovorin)

Description

Leucovorin (leucovorin calcium) is a reduced form of folic acid used in multiple therapeutic settings, primarily to enhance the efficacy or counteract the toxicity of certain chemotherapeutic agents. It is commonly used to "rescue" normal cells from the harmful effects of methotrexate, to enhance the antitumor activity of 5-fluorouracil (5-FU) in colorectal cancer, and in the treatment of folate deficiency anemia or overdosage of folic acid antagonists (e.g., trimethoprim, pyrimethamine). Leucovorin bypasses the dihydrofolate reductase step in folate metabolism, allowing for DNA and RNA synthesis to continue in cells.

Directions

Leucovorin can be administered orally, intravenously (IV), or intramuscularly (IM) depending on indication and clinical setting. Dosage and route vary significantly:

• Methotrexate rescue:

• Begin 24 hours after methotrexate infusion, typically 10–15 mg/m² every 6 hours for 10 doses, or until serum methotrexate levels are safe.

• Enhancement of 5-FU therapy:

IV leucovorin 200–500 mg/m² over 2 hours prior to 5-FU; or 20 mg/m² IV bolus immediately before 5-FU.

• Megaloblastic anemia (folate deficiency):

Oral doses of 1 mg to 5 mg daily, adjusted based on clinical response.

• Methotrexate or folic acid antagonist toxicity (e.g., overdose):

Initial IV dose of 10–100 mg, followed by repeated doses as needed based on drug levels.

Dosing must be individualized and adjusted based on methotrexate levels, renal function, and hematologic parameters.

Ingredients

Available formulations:

• Leucovorin calcium for injection (50 mg/vial, 100 mg/vial)

• Oral tablets (5 mg, 10 mg, 25 mg)

Each dose contains:

• Leucovorin calcium (calcium salt of folinic acid)

• Excipients may include lactose, microcrystalline cellulose, sodium chloride (in injection), and others depending on manufacturer

Contraindications

Leucovorin is contraindicated in patients with:

• Known hypersensitivity to leucovorin or any component of the formulation

• Pernicious anemia or other vitamin B12–deficient anemias, as it may mask hematologic symptoms while neurologic damage progresses

Cautions

• Leucovorin does not reduce the neurotoxicity of methotrexate.

• Use with 5-FU increases toxicity risk (e.g., severe diarrhea, mucositis, neutropenia); monitor closely.

• Careful dose adjustment is necessary in patients with renal impairment, especially during methotrexate rescue.

• Levoleucovorin, the active isomer, is available separately and should not be used interchangeably on a mg-to-mg basis.

Side Effects

Leucovorin is generally well tolerated. Reported side effects include:

• Allergic reactions (rash, urticaria, rare anaphylaxis)

• Gastrointestinal symptoms (nausea, vomiting, diarrhea)

• Fever

• Seizures (rare, high doses in combination therapy)

When combined with 5-FU, common toxicities include:

• Severe stomatitis and mucositis

• Neutropenia

• Diarrhea

• Hand-foot syndrome

Product Code : 13738