Reversal agent · Vitamin

Vitamin K

Also called phytonadione

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

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Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal

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Indications

Warfarin reversal for major bleeding or urgent surgery, IV with 4F-PCC (PCC acts in minutes; vitamin K sustains it)
INR over 10 without bleeding, by mouth (CHEST 2012)
Deficiency from poor intake with antibiotics, malabsorption or cholestasis
Superwarfarin rodenticide poisoning, often for months
Vitamin K deficiency bleeding in newborns, prevention and treatment (label)
Warfarin-treated patients when HIT is diagnosed (ASH 2018)

Dosing

Where	Dose
Metabolic and electrolyte boluses	Vitamin K: 5–10 mg IV slowly (no faster than 1 mg/min)

On the quick cards

Iron, vitamin B₁₂, folic acid and vitamin KNCLEX Drug Classes: Anemia, neural tube defects, newborn bleeding

Mechanism of action

Phytonadione (vitamin K1) is the cofactor for γ-glutamyl carboxylase in the liver's endoplasmic reticulum. In its reduced (hydroquinone) form it lets the enzyme carboxylate glutamate residues in the Gla domains of factors II, VII, IX and X and proteins C, S and Z, and it is oxidized to vitamin K epoxide. The γ-carboxyglutamate residues bind calcium, so the factors can attach to phosphatidylserine on activated platelets. Warfarin blocks VKORC1, which recycles the epoxide; large doses bypass the block because a warfarin-insensitive reductase (FSP1) reduces vitamin K directly.

Pharmacology

Hematologic: the INR responds first because factor VII has the shortest half-life (about 5–6 h); full correction needs new factors and fails if the liver cannot make them
Hematologic: no effect on heparin (label), LMWH, DOACs or antiplatelet drugs
Hematologic: large doses cause temporary resistance to warfarin (label)
Cardiovascular: rare anaphylactoid reactions during IV injection: flushing, hypotension, bradycardia or tachycardia, bronchospasm and arrest

Pharmacokinetics

Onset	IV 1–2 h; oral 6–10 h (labels); SC slow and erratic
Peak	IV: bleeding controlled in 3–6 h, INR often normal by 12–14 h (label); oral matches IV by 24 h (Lubetsky 2003)
Half-life	IV: 22 min, then about 2 h (DrugBank)
Distribution	Fat-soluble, carried in lipoproteins; Vd about 20 L (DrugBank); small stores; little crosses the placenta
Metabolism	Liver: epoxide cycle; side chain shortened, then glucuronidated
Elimination	Bile and urine as metabolites; almost none unchanged (label)
Bioavailability	Oral absorption needs bile salts and runs through intestinal lymph

Chemistry

2-methyl-3-phytyl-1,4-naphthoquinone (phylloquinone), C₃₁H₄₆O₂, MW 450.7: a naphthoquinone ring with a 20-carbon phytyl tail
Only the trans (E) isomer is active; USP allows up to 21% of the inactive cis (Z) isomer
A non-ionizable, water-insoluble oil, so the injection is an aqueous dispersion with a polyoxyethylated fatty acid surfactant, dextrose and benzyl alcohol 9 mg/mL (Hospira); 2 or 10 mg/mL, pH about 6.3
Light-sensitive: protect from light at all times; dilute only in NS, D5W or D5NS (label)

Adverse effects and cautions

In the one-pagers

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Sources

FDA label: Vitamin K1 injection (2025)
FDA label: phytonadione tablets (2024)
Britt 2018 (vitamin K reactions)
Mishima 2022 (FSP1)

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.