folinic acid: clinical use

Prescribing considerations

• Use with methotrexate or fluorouracil only under clinicians experienced in cancer chemotherapy.
• Coordinate folinate rescue with methotrexate exposure, serum concentrations, renal function and clinical toxicity.
• Consider delayed methotrexate elimination where renal impairment, inadequate hydration, ascites, pleural effusion or interacting medicines are present.
• Folinic acid does not prevent methotrexate nephrotoxicity caused by renal precipitation.
• Do not use folinic acid to treat cytotoxic-associated macrocytosis without establishing the cause.

Contraindications and cautions

• Hypersensitivity to folinic acid or an excipient.
• For combination with fluorouracil: any contraindication to fluorouracil, including breastfeeding.
• For combination with fluorouracil: severe diarrhoea; do not initiate or continue while gastrointestinal toxicity persists.
• Intrathecal administration is contraindicated in practice because fatal outcomes have been reported.
• Not suitable for pernicious anaemia or other vitamin B12-deficiency anaemias because neurological disease may progress despite haematological improvement.

Monitoring

• Serum methotrexate concentration and renal function during folinate rescue.
• Hydration, fluid collections and clinical evidence of delayed methotrexate elimination.
• Full blood count and gastrointestinal toxicity when combined with fluorouracil.
• Seizure frequency and, where appropriate, antiseizure medicine concentrations during and after treatment.

Clinical pharmacology

Folinic acid is a formyl derivative of tetrahydrofolate that bypasses dihydrofolate-reductase inhibition and replenishes reduced folates. With fluorouracil, it promotes a stable complex with thymidylate synthase, prolonging inhibition of DNA synthesis.

Formulation and product differences

• Sodiofolin contains disodium folinate and is an intravenous solution for injection or infusion.
• Disodium folinate has demonstrated bioequivalence to a licensed calcium-folinate reference preparation.
• Sodium content varies with vial volume and may matter where sodium intake is restricted.
• The product requires refrigerated, light-protected storage and may be diluted with sodium chloride solution; it is compatible with fluorouracil under the stated handling conditions.

Injection

Route: Parenteral

Strengths: 50 mg/mL