disodium levofolinate: clinical use

Prescribing considerations

• Use with methotrexate or fluorouracil only under direct supervision of clinicians experienced in cytotoxic therapy.
• For methotrexate rescue, consider exposure, toxicity, elimination, renal function, hydration and third-space fluid collections.
• Do not initiate or continue the fluorouracil combination while gastrointestinal toxicity is present; elderly, debilitated or previously irradiated patients may be more vulnerable.
• Disodium levofolinate does not reverse methotrexate nephrotoxicity, and excessive rescue may impair antitumour activity.

Contraindications and cautions

• Hypersensitivity to disodium levofolinate or an excipient.
• Pernicious anaemia or another anaemia caused by vitamin B12 deficiency.
• Combination with fluorouracil where fluorouracil is contraindicated or severe diarrhoea is present.
• Intrathecal administration.

Monitoring

• During methotrexate rescue: plasma methotrexate, renal function, urine output, hydration and urinary pH according to the treatment protocol.
• During fluorouracil combination therapy: gastrointestinal toxicity, hydration, blood counts and signs of infection or bleeding.
• For relevant epilepsy treatment: seizure control and, where appropriate, antiseizure medicine concentrations.

Clinical pharmacology

Levofolinic acid is the active L-isomer of folinic acid. It bypasses dihydrofolate-reductase blockade, replenishes reduced folate pools and stabilises thymidylate-synthase inhibition with fluorouracil. It is rapidly converted to active 5-methyltetrahydrofolate.

Formulation and product differences

• Ready-to-use disodium levofolinate solution for intravenous injection or infusion.
• May be diluted with sodium chloride solution or glucose solution and is compatible with fluorouracil under the specified handling conditions.
• Reported as bioequivalent to calcium levofolinate and racemic disodium folinate after intravenous administration of the same molar amount of active isomer.
• Vials are single-use, stored refrigerated and protected from light; only clear, particle-free solution should be used.

Injection

Route: Parenteral

Strengths: 50 mg/mL