Levofolic (Levoleucovorin Disodium)

Levofolic is a folate analog used in clinical situations where folate metabolism is compromised or where rescue from antifolate toxicity is required.

• Rescue from methotrexate toxicity: restores folate pools to reduce toxic effects of methotrexate.
• Folate deficiency: supplies reduced folate to patients unable to convert dietary folate.
• Supportive therapy during high‑dose chemotherapy: protects normal cells from the effects of intensive chemotherapy regimens.

• Levoleucovorin Disodium is a reduced form of folic acid that enters cells via the reduced folate carrier. It bypasses the enzymatic block created by dihydrofolate reductase inhibition, directly donating methyl groups for thymidylate and purine synthesis, thereby restoring DNA replication and cellular function during antifolate exposure or folate deficiency.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Vomiting: occasional episodes after infusion.
• Diarrhea: loose stools without severe dehydration.
• Transient rash: mild skin erythema.
• Fever: low‑grade temperature elevation.
• Headache: mild to moderate intensity.

Serious or Rare Side Effects

• Anaphylactic reaction: severe hypersensitivity requiring immediate medical intervention.
• Acute renal failure: rare impairment of kidney function.
• Severe electrolyte imbalance: uncommon disturbances in potassium or calcium levels.
• Pulmonary toxicity: rare lung inflammation.
• Hemolytic anemia: very rare destruction of red blood cells.
• Thromboembolic events: infrequent clot formation.

Levofolic should be administered with careful clinical monitoring to ensure safety and efficacy.

• Assess renal function: adjust use in patients with impaired kidney clearance.
• Monitor electrolytes: watch for potassium or calcium shifts during therapy.
• Evaluate for hypersensitivity: discontinue if severe allergic reaction occurs.
• Use caution in pregnancy: limited data, weigh benefits against potential risks.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Levofolic can interact with other medications that affect folate metabolism or renal excretion.

Major Interactions (Avoid)

• High‑dose methotrexate: concurrent use without appropriate timing may reduce rescue effect.
• Anticonvulsants (e.g., phenytoin, carbamazepine): may increase folate depletion.

Moderate Interactions (Monitor Closely)

• NSAIDs: may affect renal clearance of leucovorin.
• Loop diuretics: can exacerbate electrolyte disturbances.
• Vitamin B12 supplements: may alter folate utilization dynamics.