PHYTONADIONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHYTONADIONE (PHYTONADIONE).

How it works

Vitamin K is a cofactor for the microsomal enzyme gamma-glutamyl carboxylase, which catalyzes the post-translational carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) in vitamin K-dependent proteins, including clotting factors II, VII, IX, X, and proteins C and S. This carboxylation is essential for calcium binding and the biological activity of these proteins.

What the body does with it

Metabolism	Phytonadione is rapidly metabolized in the liver via side-chain oxidation and conjugation to more polar metabolites, which are excreted in bile and urine.
Excretion	Primarily hepatic metabolism; only about 5% excreted unchanged in urine; major elimination via bile and feces as metabolites.
Half-life	Terminal half-life is approximately 1.5–2 hours for intravenous administration; for oral, half-life is about 1.5–2.5 hours, but may be prolonged in patients with liver disease or vitamin K deficiency.
Protein binding	Highly protein bound (>99%) primarily to albumin; also binds to lipoproteins.
Volume of Distribution	Approximately 0.3–0.5 L/kg, indicating distribution largely confined to plasma and extracellular fluid; does not readily cross blood-brain barrier.
Bioavailability	Oral bioavailability is low and variable (approximately 50%) due to limited absorption and first-pass hepatic metabolism; intramuscular bioavailability is nearly complete; intravenous yields 100%.
Onset of Action	Intravenous: 1–2 hours; intramuscular: 3–8 hours; oral: 6–12 hours; onset depends on absorption and hepatic synthesis of clotting factors.
Duration of Action	Duration of effect on clotting factor synthesis is 24–36 hours following IV or IM administration; oral duration is similar, but effects may persist longer in patients with impaired liver function.

Classification & Brands

Dosing & administration

1-10 mg intramuscularly or subcutaneously, repeated in 12-48 hours if necessary; for anticoagulant reversal, 2.5-10 mg orally or parenterally.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No specific Child-Pugh based adjustment; use with caution in severe hepatic impairment due to potential altered metabolism.
Pediatric use	Neonates: 1 mg intramuscularly once; Infants and Children: 1-2 mg intramuscularly or subcutaneously, may repeat after 12-24 hours.
Geriatric use	No specific adjustment; monitor for bleeding risk due to polypharmacy and comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHYTONADIONE (PHYTONADIONE).

Breastfeeding	Phytonadione is excreted into breast milk in minimal amounts; M/P ratio not established. Considered compatible with breastfeeding; no adverse effects reported in infants.
Teratogenic Risk	First trimester: No evidence of teratogenicity in human studies; animal studies show no harm. Second and third trimesters: Vitamin K deficiency can cause fetal hemorrhage; supplementation is protective. No known teratogenic risk.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Intravenous administration of Phytonadione has been associated with severe reactions, including fatalities, resembling hypersensitivity or anaphylaxis. These reactions have occurred despite dilution and slow administration. The intravenous route should be reserved for severe cases and when the subcutaneous route is not feasible.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to Phytonadione or any component of the formulation","Use of large doses in patients with severe liver disease when the prothrombin time is not prolonged (ineffective and may cause hyperbilirubinemia)"]

Clinical Precautions

Precautions

["Intravenous administration may cause severe anaphylactoid reactions; reserve for serious situations and administer slowly.","Monitor prothrombin time (PT) and international normalized ratio (INR) closely during therapy.","Use with caution in patients with severe hepatic disease as response may be diminished.","Not effective for reversal of the anticoagulant effect of heparin or direct oral anticoagulants (DOACs).","Parenteral formulations may contain benzyl alcohol; avoid in premature neonates due to risk of 'gasping syndrome'."]

Clinical Tips & Counseling

Drug interactions

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PHYTONADIONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHYTONADIONE (PHYTONADIONE).

How it works

What the body does with it

Metabolism	Phytonadione is rapidly metabolized in the liver via side-chain oxidation and conjugation to more polar metabolites, which are excreted in bile and urine.
Excretion	Primarily hepatic metabolism; only about 5% excreted unchanged in urine; major elimination via bile and feces as metabolites.
Half-life	Terminal half-life is approximately 1.5–2 hours for intravenous administration; for oral, half-life is about 1.5–2.5 hours, but may be prolonged in patients with liver disease or vitamin K deficiency.
Protein binding	Highly protein bound (>99%) primarily to albumin; also binds to lipoproteins.
Volume of Distribution	Approximately 0.3–0.5 L/kg, indicating distribution largely confined to plasma and extracellular fluid; does not readily cross blood-brain barrier.
Bioavailability	Oral bioavailability is low and variable (approximately 50%) due to limited absorption and first-pass hepatic metabolism; intramuscular bioavailability is nearly complete; intravenous yields 100%.
Onset of Action	Intravenous: 1–2 hours; intramuscular: 3–8 hours; oral: 6–12 hours; onset depends on absorption and hepatic synthesis of clotting factors.
Duration of Action	Duration of effect on clotting factor synthesis is 24–36 hours following IV or IM administration; oral duration is similar, but effects may persist longer in patients with impaired liver function.

Classification & Brands

Dosing & administration

1-10 mg intramuscularly or subcutaneously, repeated in 12-48 hours if necessary; for anticoagulant reversal, 2.5-10 mg orally or parenterally.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No specific Child-Pugh based adjustment; use with caution in severe hepatic impairment due to potential altered metabolism.
Pediatric use	Neonates: 1 mg intramuscularly once; Infants and Children: 1-2 mg intramuscularly or subcutaneously, may repeat after 12-24 hours.
Geriatric use	No specific adjustment; monitor for bleeding risk due to polypharmacy and comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHYTONADIONE (PHYTONADIONE).

Breastfeeding	Phytonadione is excreted into breast milk in minimal amounts; M/P ratio not established. Considered compatible with breastfeeding; no adverse effects reported in infants.
Teratogenic Risk	First trimester: No evidence of teratogenicity in human studies; animal studies show no harm. Second and third trimesters: Vitamin K deficiency can cause fetal hemorrhage; supplementation is protective. No known teratogenic risk.
Fetal Monitoring