Levofolic (Levoleucovorin Disodium)

Levofolic is used as a rescue agent in clinical situations involving antifolate chemotherapy.

• Methotrexate toxicity: Reduces toxic effects associated with methotrexate therapy.
• High‑dose methotrexate rescue: Restores folate pools after high‑dose methotrexate administration.
• Chemotherapy supportive care: Supports patients receiving antifolate‑based chemotherapy regimens.

• Levoleucovorin disodium supplies a reduced folate that bypasses dihydrofolate reductase inhibition, allowing direct participation in folate‑dependent nucleotide synthesis. By replenishing tetrahydrofolate pools, it restores DNA synthesis in normal cells and diminishes the cytotoxic impact of antifolate drugs such as methotrexate, thereby reducing systemic toxicity.

Levofolic may be associated with a range of adverse reactions following intravenous administration.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Vomiting: occasional emesis after infusion.
• Diarrhea: loose stools occurring within 24 hours.
• Fever: transient low‑grade temperature rise.
• Headache: mild cranial discomfort.
• Injection site pain: local discomfort at the infusion site.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction requiring immediate medical attention.
• Acute renal failure: sudden loss of kidney function.
• Hepatotoxicity: elevated liver enzymes indicating liver stress.
• Severe neutropenia: marked reduction in white blood cells.
• Thromboembolic events: rare clot formation.
• Hypersensitivity syndrome: multi‑system allergic response.

Before using Levofolic, clinicians should consider several safety measures.

• Renal function: assess creatinine clearance and adjust use in renal impairment.
• Hepatic function: evaluate liver enzymes, especially in patients with pre‑existing liver disease.
• Pregnancy status: avoid use unless benefits outweigh potential risks.
• Concomitant antifolates: monitor closely when other folate pathway agents are co‑administered.
• Electrolyte balance: correct significant abnormalities prior to infusion.
• Store at ambient temperature: keep in original packaging, protect from moisture and direct sunlight.

Levofolic can interact with other medicines that affect folate metabolism or renal clearance.

Major Interactions (Avoid)

• High‑dose methotrexate: concurrent use without proper timing may reduce rescue effectiveness.
• Nephrotoxic agents (e.g., cisplatin): combined renal stress can increase toxicity.

Moderate Interactions (Monitor Closely)

• NSAIDs: may impair renal excretion of levoleucovorin.
• Proton pump inhibitors: potential alteration of folate absorption (though less relevant for IV).
• Sulfonamides: competitive inhibition of folate pathways.
• Anticonvulsants (e.g., phenytoin): may increase folate turnover.
• Diuretics: affect fluid balance during infusion.