Leucovorin Calcium
Leucovorin calcium (also known as folinic acid or citrovorum factor) is a reduced folic acid derivative primarily used in veterinary medicine as a **rescue agent** or **antidote**. * **Primary Indication**: It is used to reverse or prevent hematologic toxicity (such as bone marrow suppression, macrocytic anemia, and neutropenia) associated with dihydrofolate reductase inhibitors (e.g., pyrimethamine, trimethoprim, or ormetoprim). * **Methotrexate Rescue**: While routinely used in human medicine as a rescue agent for high-dose methotrexate chemotherapy, it is rarely used for this purpose in veterinary medicine, except in cases of accidental methotrexate overdose. * **Clinical Pearl**: Unlike standard folic acid, leucovorin does *not* require the enzyme dihydrofolate reductase to become biologically active. This allows it to bypass the enzymatic blockade caused by folic acid antagonists, directly supplying the necessary folates for cellular function.
Mechanism: Leucovorin is a reduced form of folic acid that acts as a direct coenzyme in cellular metabolism. * **Bypassing DHFR**: It does not require conversion by **dihydrofolate reductase (DHFR)** to become biologically active. * **Active Metabolite**: It is converted in the body to active reduced forms, predominantly **5-methyltetrahydrofolate (5-methyl THF)**. * **DNA Synthesis**: These reduced folates act as coenzymes in the synthesis of **purine and pyrimidine nucleotides** → essential for **DNA synthesis** and the maintenance of normal **erythropoiesis** (red blood cell production). * **Enzyme Inhibition**: Leucovorin inhibits **thymidylate synthase** by stabilizing the binding of fluorodeoxyuridylic acid to the enzyme. This mechanism potentiates both the antineoplastic activity and the toxicity of **fluorouracil (5-FU)**.
Dosing by species
- Folate deficiency associated with pyrimethamine use · 5-15 mg (total dose) PO or parenterally once daily · PO/Parenteral · q24h
- Bone marrow suppression associated with pyrimethamine or trimethoprim/sulfa · 5 mg once daily · Not specified · q24h
- To prevent bone marrow toxicity associated with pyrimethamine · 1 mg/kg once daily · Not specified · q24h
- Methotrexate overdose · 25-200 mg/m2 parenterally every 6 hours until methotrexate levels are less than 1 X 10 -8 M · Parenteral · q6h · Until methotrexate levels are < 1 X 10^-8 M · Most effective if given within 48 hours of overdose.
- Macrocytic anemia and neutropenia associated with pyrimethamine and/or trimethoprim (especially in pregnant mares) · 0.1-0.3 mg/kg PO once daily · PO · q24h · A more practical approach would be to ensure that the horse receives green hay or pasture (high tetrahydrofolate levels in green roughage).
- Folate deficiency associated with pyrimethamine use · 5-15 mg (total dose) PO or parenterally once daily · PO/Parenteral · q24h
- Methotrexate overdose · 25-200 mg/m2 parenterally every 6 hours until methotrexate levels are less than 1 X 10 -8 M · Parenteral · q6h · Until methotrexate levels are < 1 X 10^-8 M · Most effective if given within 48 hours of overdose. Dose is dependent on serum methotrexate concentration.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Known intolerance or hypersensitivity to leucovorin
Adverse effects
- Gastrointestinal effects (noted in humans with oral administration)
- Seizures (very rare, noted in humans)
- Hypersensitivity reactions (very rare, noted in humans)
Drug interactions
- Barbiturates, Primidone, Phenytoin · Large doses of leucovorin may reduce the antiseizure efficacy of these agents.
- Fluorouracil (5-FU) · Leucovorin may increase both the antineoplastic efficacy and toxicity of 5-FU.
- Trimethoprim, Ormetoprim, Pyrimethamine · Leucovorin may reduce their efficacy somewhat; however, protozoa cannot utilize leucovorin, preserving the antimicrobial effect against them.
Monitoring
- Complete Blood Count (CBC)
- Methotrexate serum levels (if used for methotrexate overdoses; may require contacting a local human hospital)
Overdose
Except in situations where drug interactions are possible (e.g., with fluorouracil or antiseizure medications), an inadvertent overdose is unlikely to be of clinical concern.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.