Leucovorin (Folinic Acid)

Leucovorin is employed in clinical settings where folate pathways are compromised or need support during chemotherapy.

• Methotrexate toxicity: provides rescue therapy that reduces cellular damage caused by methotrexate overdose.
• 5‑Fluorouracil‑based chemotherapy: enhances efficacy and reduces toxicity when given as an adjunct.
• Folate deficiency: restores normal folate levels in patients with inadequate dietary intake or malabsorption.

• Folinic Acid supplies a reduced form of folate that bypasses the dihydrofolate reductase step, directly entering the tetrahydrofolate pool. This restores nucleotide synthesis and methylation reactions, allowing normal DNA replication and repair despite inhibition of folate metabolism by antifolate agents such as methotrexate or 5‑fluorouracil.

Leucovorin may be associated with a range of adverse reactions, most of which are mild and reversible.

Common Side Effects

• Nausea: mild to moderate upset stomach.
• Vomiting: occasional episodes after administration.
• Diarrhea: loose stools that resolve with continued therapy.
• Rash: transient skin erythema or itching.
• Fever: low‑grade temperature elevation.
• Headache: mild discomfort not requiring intervention.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction with airway compromise.
• Acute renal failure: sudden loss of kidney function.
• Severe neutropenia: marked drop in white blood cells increasing infection risk.
• Thromboembolic events: blood clots in veins or arteries.

Before using Leucovorin, clinicians should evaluate patient history and monitor for specific risks.

• Renal impairment: adjust dosing or monitor renal function closely.
• Hepatic disease: assess liver enzymes and consider dose modification.
• Pregnancy: use only if potential benefit justifies potential risk to the fetus.
• Breastfeeding: weigh benefits against possible infant exposure through milk.
• Concomitant chemotherapy: coordinate timing to avoid antagonism of anticancer effect.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze.

Leucovorin can influence the activity of several co‑administered drugs.

Major Interactions (Avoid)

• High‑dose methotrexate: may reduce therapeutic efficacy if given simultaneously.
• Antifolate agents other than methotrexate: can diminish intended cytotoxic effect.

Moderate Interactions (Monitor Closely)

• Trimethoprim‑sulfamethoxazole: may increase risk of hematologic toxicity.
• Phenytoin: possible alteration of folate metabolism requiring monitoring.
• Vitamin B12 deficiency: concurrent deficiency may blunt response, necessitating supplementation.