Leucovorin (Calcium Folinate Pentahydrate)

Leucovorin is used in clinical settings that involve folate‑antagonist chemotherapy and folate deficiency.

• High‑dose methotrexate therapy: provides rescue to reduce life‑threatening toxicity.
• Fluoropyrimidine chemotherapy (e.g., 5‑FU, capecitabine): decreases mucosal and hematologic toxicity.
• Folate deficiency: supplies reduced folate for patients unable to convert folic acid.
• Certain hematologic disorders: supports bone‑marrow recovery during intensive treatment.

• Leucovorin delivers a reduced form of folate that bypasses dihydrofolate reductase inhibition, directly replenishing intracellular tetrahydrofolate pools. This restoration enables normal synthesis of purines and thymidylate, supporting DNA replication and cell division even in the presence of antifolate agents.

Leucovorin is generally well tolerated, but adverse reactions can occur.

Common Side Effects

• Nausea or vomiting
• Flushing or warmth sensation
• Low-grade fever
• Mild hypotension
• Transient rash or itching

Serious or Rare Side Effects

• Anaphylactic or severe allergic reactions
• Acute renal impairment
• Severe hypotension requiring intervention
• Hemolytic anemia in susceptible individuals

Leucovorin should be administered with careful clinical monitoring.

• Renal function assessment: evaluate creatinine clearance before dosing.
• Electrolyte monitoring: watch for changes in potassium and magnesium.
• Hypersensitivity: discontinue if signs of severe allergic reaction appear.
• Pregnancy: use only if potential benefit justifies potential risk to the fetus.
• Hepatic impairment: consider dose adjustment in severe liver disease.
• Store at 2‑8 °C: keep refrigerated, protect from light, do not freeze.

Leucovorin may interact with other drugs affecting folate metabolism or renal function.

Major Interactions (Avoid)

• Concurrent high‑dose antifolate agents (e.g., pemetrexed) that may negate rescue effect.
• Nephrotoxic drugs (e.g., aminoglycosides) that increase risk of renal injury.

Moderate Interactions (Monitor Closely)

• Fluoropyrimidines (5‑FU, capecitabine): monitor for enhanced toxicity.
• Cytarabine: observe for additive myelosuppression.
• Cisplatin: assess renal function closely.
• Warfarin: folate may affect INR, require more frequent monitoring.