Pharmacology · Anticoagulant reversal agents

Phytomenadione (vitamin K1) !

Vitamin K1 as a medicine. It lets the liver make working clotting factors again: it reverses warfarin and prevents bleeding in newborns.

Updated 2026-11-01

Class: Anticoagulant reversal agents
Enzyme: Vitamin K-dependent gamma-glutamyl carboxylase (GGCX), which uses vitamin K as its cofactor
ATC code: B02BA01
WHO Model List of Essential Medicines

Also called: phytonadione, vitamin K1

Vitamin K-dependent gamma-glutamyl carboxylase (GGCX), which uses vitamin K as its cofactorPhytomenadione (vitamin K1)

The figure shows human gamma-glutamyl carboxylase holding vitamin K1 hydroquinone (the active, reduced form of phytomenadione) and a piece of factor IX.

Target in 3D: Vitamin K-dependent gamma-glutamyl carboxylase (GGCX), which uses vitamin K as its cofactor. PDB structure 9BVK (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Vitamin K is the cofactor of gamma-glutamyl carboxylase, a liver enzyme that adds carboxyl groups to glutamic acid residues of factors II, VII, IX and X (and proteins C and S). Only carboxylated factors can bind calcium and work. Warfarin and vitamin K deficiency leave the factors unfinished; phytomenadione supplies vitamin K again, so the liver releases working factors. It is not a clotting agent itself and its effect is not immediate.

Phytomenadione restores the liver's supply of vitamin K
Gamma-glutamyl carboxylase finishes factors II, VII, IX and X
Working factors are released into the blood over hours
The INR falls and bleeding risk drops

Pharmacokinetics

Absorption: Given by mouth or by injection; the injection is preferred under the skin.
Distribution: Concentrated in the liver at first; it crosses the placenta.
Metabolism: Little is known about its fate; almost no unchanged vitamin K appears in bile or urine.
Onset and duration: Not immediate: the INR improves over about 1 to 8 hours.

Indications

Bleeding risk or bleeding from coumarin anticoagulants such as warfarin (too high INR). Anticoagulant poisoning (warfarin and superwarfarins) →
Prevention and treatment of vitamin K deficiency bleeding in newborns. Vitamin K deficiency bleeding of the newborn →
Low prothrombin from poor vitamin K absorption (obstructive jaundice, coeliac disease, intestinal resection, cystic fibrosis) or from antibiotics.

Adverse effects

Common

Pain, swelling and tenderness at the injection site
Flushing, sweating, dizziness, altered taste
Skin reactions after injection, sometimes weeks or months later

Contraindications

Hypersensitivity to any component of the product

Key interactions

Warfarin and other coumarins: Reverses their effect; large amounts can cause temporary resistance when the anticoagulant is restarted.
Heparin: No effect: phytomenadione does not reverse heparin.
Direct oral anticoagulants (apixaban, rivaroxaban, dabigatran): No useful effect on their anticoagulant activity.

What is monitored

INR, repeated over the following hours
Signs of bleeding
Signs of anaphylaxis during and after intravenous use: blood pressure, breathing, skin

Administration and safety

The injection is given under the skin whenever possible; when the IV route cannot be avoided it is injected very slowly
The emulsion is protected from light at all times
Resuscitation equipment is at hand for intravenous use
In serious bleeding it is combined with faster products (prothrombin complex concentrate or plasma), because it acts only after hours

Nursing care

Check the INR before and after giving it
Watch closely for flushing, breathing difficulty, low blood pressure or chest pain during an IV injection
In newborns, record the prophylactic dose given after birth
Teach patients on warfarin that sudden changes in vitamin K-rich foods (green leafy vegetables) move the INR

Pregnancy and breastfeeding

It crosses the placenta; when it is needed in pregnancy, a preservative-free product is preferred.

Test yourself

Think of the answer, then tap the question to see it.

Which clotting factors need vitamin K, and what enzyme uses it?

Factors II, VII, IX and X (and proteins C and S); gamma-glutamyl carboxylase uses vitamin K to carboxylate them.

Why is vitamin K alone not enough for life-threatening bleeding on warfarin?

The INR takes hours to improve because the liver must make new factors; prothrombin complex concentrate or plasma replace them faster.

Which route of vitamin K injection carries the highest risk of severe hypersensitivity?

Intravenous (and intramuscular) injection; fatal anaphylaxis has occurred, so the subcutaneous route is preferred when possible.

Does vitamin K reverse heparin?

No. Heparin acts through antithrombin, not through vitamin K; protamine is its antidote.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - PHYTONADIONE injection, emulsion (DailyMed (U.S. National Library of Medicine), 2026); Phytonadione Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Phytonadione: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); 9BVK: Vitamin K-dependent gamma-carboxylase with factor IX propeptide and glutamate-rich region and with vitamin K hydroquinone (RCSB Protein Data Bank, 2025).

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Representative model, for educational purposes only.