Levofolene (Levoleucovorin)

Levofolene (levoleucovorin) is used in clinical settings to rescue patients from antifolate‑induced toxicity and to support folate metabolism.

• High‑dose methotrexate rescue: restores folate pools and reduces methotrexate‑related toxicity.
• 5‑fluorouracil adjunct therapy: enhances tolerability of 5‑FU‑based regimens by supplying reduced folate.
• Folate deficiency prevention: corrects folate deficiency in patients receiving folate‑depleting chemotherapy.

• Levoleucovorin provides a reduced form of folate that bypasses the dihydrofolate reductase blockade caused by antifolate agents. By entering the folate cycle downstream of the inhibited step, it restores the synthesis of thymidine and purine nucleotides, allowing DNA replication and repair to continue and thereby reducing the cytotoxic impact of drugs such as methotrexate and 5‑fluorouracil.

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

Common Side Effects

• Nausea: mild to moderate upset stomach.
• Vomiting: occasional episodes after dosing.
• Diarrhea: transient loose stools.
• Rash: mild skin erythema.
• Headache: occasional dull headache.
• Fatigue: feeling of tiredness.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction requiring immediate medical attention.
• Neutropenia: marked reduction in white blood cells.
• Thrombocytopenia: low platelet count leading to bleeding risk.
• Renal dysfunction: impaired kidney function.
• Hepatic toxicity: elevated liver enzymes.
• Severe skin reactions: such as Stevens‑Johnson syndrome.

Levofolene should be used with appropriate clinical monitoring.

• Renal function: assess baseline and monitor during therapy.
• Hepatic function: evaluate liver enzymes before and during treatment.
• Concurrent chemotherapy: coordinate timing to avoid antagonism.
• Pregnancy: use only if clearly needed after risk‑benefit assessment.
• Pediatric patients: dose may require adjustment based on weight and age.
• Store at ambient temperature: keep in the original pack, protect from moisture and light.

Levofolene may interact with other medicines; monitoring is advised.

Major Interactions (Avoid)

• High‑dose folic acid supplements: may diminish intended rescue effect.
• Cytarabine: concurrent use can increase toxicity.

Moderate Interactions (Monitor Closely)

• NSAIDs: may affect renal clearance of levoleucovorin.
• Penicillins: can increase renal excretion, altering levels.
• Proton pump inhibitors: may alter gastrointestinal absorption.
• Sulfonamides: potential additive effect on folate pathways.