Isovorin (Levoleucovorin)

Isovorin is used as a folate‑based adjunct in chemotherapy regimens and as a rescue agent after high‑dose methotrexate therapy.

• Colorectal cancer: enhances the efficacy of 5‑fluorouracil and improves tumor response.
• Other solid tumours: supports 5‑fluorouracil‑based regimens in gastric, pancreatic and head‑and‑neck cancers.
• High‑dose methotrexate toxicity: rescues normal cells and reduces systemic toxicity after methotrexate administration.

• Levoleucovorin provides a reduced folate cofactor that stabilises the ternary complex between 5‑fluorouracil‑derived metabolites and thymidylate synthase, thereby increasing inhibition of DNA synthesis in tumour cells. In the context of methotrexate therapy, it bypasses dihydrofolate reductase inhibition, restoring folate‑dependent pathways in healthy tissues and mitigating drug‑induced toxicity.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Vomiting: occasional emesis following infusion.
• Rash: transient skin erythema or mild pruritus.
• Flushing: brief warmth or redness of the face and neck.
• Elevated liver enzymes: mild, reversible increase in transaminases.
• Fatigue: temporary feeling of tiredness.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction requiring immediate medical attention.
• Renal toxicity: impaired kidney function, especially with high‑dose regimens.
• Severe hepatic dysfunction: marked elevation of liver enzymes or jaundice.
• Neutropenia: significant reduction in white blood cell count.
• Thrombocytopenia: low platelet count leading to bleeding risk.
• Stevens‑Johnson syndrome: rare severe skin reaction.

Levoleucovorin should be used with careful clinical monitoring.

• Renal function: assess creatinine clearance before and during therapy.
• Hepatic function: monitor liver enzymes regularly.
• Hypersensitivity: observe for signs of allergic reaction during infusion.
• High‑dose methotrexate: coordinate timing to ensure optimal rescue effect.
• Dose adjustment: consider reduced dosing in patients with renal impairment.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Levoleucovorin may interact with other medications that affect folate pathways or renal clearance.

Major Interactions (Avoid)

• High‑dose methotrexate: concurrent use without proper timing can increase toxicity.
• Other folate antagonists (e.g., pemetrexed): may diminish therapeutic benefit.
• Trimethoprim‑sulfamethoxazole: can potentiate folate deficiency.

Moderate Interactions (Monitor Closely)

• NSAIDs: may affect renal function, requiring monitoring.
• Nephrotoxic agents (e.g., cisplatin, aminoglycosides): increase risk of renal impairment.
• Drugs influencing renal clearance (e.g., probenecid): may alter levoleucovorin levels.