Vitamin K (antidote)

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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

• 2 mg/0.2 mL ampoules
• 10 mg/1 mL ampoules

Toxicological Indications

• Significant coumadin-induced coagulopathy:
  • Therapeutic over-warfarinisation.
  • Intentional warfarin overdose.
  • Ingestion of long-acting anticoagulant rodenticides (e.g., brodifacoum).

Contraindications

• Known hypersensitivity.

Mechanism of Action

• Phytomenadione is a synthetic fat-soluble analogue of natural vitamin K1, essential for the synthesis of clotting factors II, VII, IX, and X.
• Coumadin anticoagulants inhibit vitamin K1 2,3-epoxide reductase, preventing the active form of vitamin K and impairing clotting factor production. High doses of vitamin K can overcome this inhibition and restore normal clotting factor levels.

Pharmacokinetics

• Oral bioavailability: Variable (~50%), dependent on bile salts.
• Metabolism: Rapidly metabolised by the liver.
• Half-life: ~2 hours.
• Effect timing: Increase in coagulation factors is delayed by 6–12 hours after oral and 3–6 hours after IV administration.

Administration

• Therapeutic over-warfarinisation: Refer to Appendix 5 for specific guidelines.
• Warfarin overdose:
  • No need for anticoagulation if the patient unintentionally ingested warfarin.
  • Dosage: 5 mg orally or IV daily for 2 days.
  • INR should be checked at 48 hours.
• Therapeutic anticoagulation requirement:
  • Monitor INR closely (every 6 hours).
  • Administer 0.5–2 mg IV if INR >5.
  • Repeat doses as necessary if INR remains or returns to >5.
  • Start heparin if INR falls <2 and there is an absolute indication for anticoagulation (e.g., mechanical heart valve).
• Long-acting anticoagulant rodenticide ingestion:
  • Requires large daily oral doses for weeks to months if anticoagulation develops.
  • Initial dosing varies and is determined with repeated INR tests.
  • Requires close monitoring to ensure compliance and safe discontinuation.
  • Emergency: For active or high-risk bleeding (INR >9), administer prothrombin complex concentrate and fresh frozen plasma, in addition to vitamin K.

Adverse Drug Reactions and Management

• Minor reactions: Facial flushing, chest tightness, dyspnoea, dizziness with IV administration.
• Rare reactions: Anaphylaxis with IV administration.
• Warfarin resistance: Can lead to over-correction of anticoagulation.
  • Management: Use heparin until warfarin resistance resolves, then reintroduce warfarin.

Specific Considerations

• Pregnancy: No restrictions on use.
• Paediatric: Treat suspected warfarin ingestion (>0.5 mg/kg) with a single 5 mg oral dose to avoid repeated blood tests.

Handy Tips

• Administration route: Do not use intramuscular injections.
• Oral use: The injectable formulation is suitable for oral administration.
• Unintentional child ingestion: One-time accidental ingestion of anticoagulant rodenticide does not usually require medical assessment or vitamin K therapy.

Pitfalls

• Excessive doses: May cause warfarin resistance in patients needing continued anticoagulation, requiring heparinisation before reintroducing warfarin.
• Premature vitamin K administration: Can be problematic before anticoagulant effects are confirmed in adults with rodenticide overdose.

Controversies

• Threshold INR: Debate on INR level for vitamin K administration in over-warfarinisation or overdose situations.
• Duration of therapy: Prolonged administration (2–7 days) may be necessary for self-poisoning cases due to the long half-life of warfarin.