Vitamin K (Phytonadione)
Mephyton · AquaMEPHYTON
Fat-soluble vitamin — warfarin reversal / factor synthesis cofactor
Cofactor for γ-carboxylation of factors II, VII, IX, X and proteins C/S. Restores warfarin-inhibited synthesis over hours.
Indications
- •Warfarin reversal
- •Vitamin K deficiency (malnutrition, malabsorption, biliary obstruction)
- •Newborn prophylaxis
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Non-urgent warfarin (high INR, no bleed) | 1–2.5 mg PO | — |
| Major bleed | 5–10 mg IV slow (with 4F-PCC) | — |
| Newborn prophylaxis | 0.5–1 mg IM at birth | — |
Pharmacokinetics
Onset: IV 6–8 h, PO 24 h to meaningful INR change. Give with PCC/FFP for immediate reversal.
Side effects
- !IV anaphylactoid reaction (give slow, diluted)
- !Warfarin resistance for days after large doses
Contraindications
- ×Rapid IV push (anaphylactoid risk)
Clinical pearls
- ★Vitamin K alone is SLOW (hours) — pair with 4F-PCC (or FFP) for emergent reversal.
- ★IV route reserved for serious bleeding, given slowly/diluted — anaphylactoid risk.
- ★Large doses cause days of warfarin resistance — dose to the clinical need.
Other drugs in Coagulation Related
- Heparin (unfractionated)
Activates antithrombin → inactivates IIa (thrombin) and Xa.
- Tranexamic Acid (TXA)
Reversibly binds plasminogen, blocking conversion to plasmin → preserves fibrin clot.
- Protamine Sulfate
Strongly basic (positive-charge) protein binds to highly acidic (negative-charge) heparin → inactive ionic complex → renal excretion. 1 mg protamine neutralizes ~100 units heparin.
- DDAVP (Desmopressin)
Selective V2 agonist (renal water retention + Factor VIII/vWF release from endothelial Weibel-Palade bodies). NO V1 vasopressor activity at therapeutic dose.
- Warfarin
Inhibits vitamin K epoxide reductase (VKORC1) → depletes reduced vitamin K → ↓ synthesis of factors II, VII, IX, X and proteins C/S. Full effect takes days (waits for existing factor decay).
- Enoxaparin
Antithrombin-mediated inhibition, weighted toward factor Xa over IIa (~3.8:1). More predictable than UFH — no routine monitoring.
- Dalteparin
Antithrombin-mediated factor Xa > IIa inhibition. Similar profile to enoxaparin; preferred LMWH in cancer-associated VTE (CLOT trial).
Suggested reading
- •Miller's Anesthesia, 9e
- •FDA package insert
