Leucovorin (Calcium Folinate)

Leucovorin is used in clinical situations that involve folate pathway disruption or increased folate demand.

• Methotrexate toxicity rescue: reduces toxic effects of high‑dose methotrexate by restoring reduced folate pools.
• Folate deficiency: replenishes folate stores in patients with inadequate dietary intake or malabsorption.
• Chemotherapy adjunct: enhances efficacy and reduces toxicity of selected antimetabolite regimens such as 5‑fluorouracil‑based protocols.

• Leucovorin provides a reduced form of folate that bypasses the dihydrofolate reductase (DHFR) step inhibited by drugs such as methotrexate. By directly supplying 5‑methyltetrahydrofolate, it restores the folate cofactor pool needed for thymidylate and purine synthesis, allowing DNA replication and cell proliferation to continue despite DHFR blockade. This rescue effect also supports normal tissue recovery while allowing antimetabolite agents to retain antitumor activity.

Leucovorin may be associated with a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Nausea: mild gastrointestinal upset.
• Vomiting: occasional emesis.
• Diarrhea: loose stools.
• Skin rash: erythematous or maculopapular eruptions.
• Fever: low‑grade temperature elevation.
• Transient elevation of liver enzymes: mild AST/ALT rise.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction requiring immediate medical attention.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Acute renal failure: sudden loss of kidney function.
• Hematologic abnormalities: pancytopenia or severe neutropenia.
• Pulmonary toxicity: interstitial pneumonitis.

When using Leucovorin, clinicians should observe several precautionary measures to ensure safe administration.

• Renal impairment: adjust monitoring as reduced clearance may increase exposure.
• Hepatic dysfunction: observe liver function tests because metabolism occurs hepatically.
• Pregnancy: use only if potential benefit justifies risk, as data are limited.
• Concomitant chemotherapy: coordinate timing to avoid antagonizing antimetabolite efficacy.
• Allergic history: assess for prior hypersensitivity to folinic acid preparations.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze.

Leucovorin can interact with other medicines, altering efficacy or safety.

Major Interactions (Avoid)

• High‑dose methotrexate: concurrent use without appropriate timing may diminish rescue effect.
• Antifolates (pemetrexed, trimetrexate): may reduce antitumor activity if given simultaneously.

Moderate Interactions (Monitor Closely)

• Cytarabine: potential additive myelosuppression, monitor blood counts.
• Sulfonamides: may increase risk of hypersensitivity reactions.
• Oral contraceptives: folate supplementation can affect hormone levels, observe efficacy.
• Vitamin B12 deficiency: folate may mask hematologic signs, monitor B12 status.