Folinic acid (antidote)

#completed #carded

Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Presentations

• Calcium folinate 15 mg tablets, 15 mg/2 mL ampoules, 50 mg/5 mL vials/ampoules, 100 mg/10 mL vials/ampoules, 300 mg/30 mL vials.

Toxicological Indications

• Supratherapeutic methotrexate ingestion:
  • Occurs with accidental daily dosing rather than weekly.
  • Indications:
    • Clinical features of methotrexate toxicity.
    • Daily administration of weekly dose >3 consecutive days.
• Single acute methotrexate overdose:
  • Empiric use if >500 mg ingested or if methotrexate levels unavailable.
  • Consider if <500 mg ingested and no methotrexate levels available within 24 hours.
• Adjunctive therapy for methanol poisoning.
• Massive pyrimethamine or trimethoprim poisoning.

Contraindications

• Known hypersensitivity.

Mechanism of Action

• Reduced biologically active folic acid essential for DNA/RNA synthesis.
• Bypasses methotrexate inhibition of dihydrofolate reductase, restoring DNA/RNA synthesis.
• Enhances formate elimination in methanol poisoning.

Pharmacokinetics

• Oral bioavailability: ~100% at 15 mg; lower with higher doses.
• Volume of distribution: 13.6 L; elimination half-life: 35 min.
• Active metabolite (5-methyltetrahydrofolate): volume of distribution: 40 L; half-life: >400 min.

Administration

Methotrexate Overdose

• Dose: 15 mg PO, IM, or IV every 6 hours.
• Duration:
  • Acute overdose: Continue for at least 3 days or until serum methotrexate <0.05 μmol/L.
  • Chronic toxicity: Continue for at least 3 days and until serum methotrexate <0.05 μmol/L.

Methanol Poisoning

• Dose: 2 mg/kg IV every 6 hours.
• Duration: Continue until definitive treatment of poisoning.

Adverse Drug Reactions

• Rare: Anaphylaxis, seizures.
• Hypercalcaemia with rapid IV administration (>160 mg/min).

Specific Considerations

• Pregnancy: No restrictions.
• Paediatric use: Dosing for oral methotrexate overdose not determined.

Handy Tip

• Rarely needed for acute single methotrexate overdose.

Pitfall

• Substituting folic acid for folinic acid (ineffective for methotrexate toxicity).

Controversies

• Indications for use following single acute methotrexate overdose.
• Duration of treatment for chronic toxicity (may require continuation until bone marrow recovery).
• Efficacy of adjunctive folinic acid in methanol poisoning.