MENADIONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MENADIONE (MENADIONE).

How it works

Menadione is a synthetic derivative of vitamin K that serves as a cofactor for the post-translational carboxylation of glutamic acid residues in vitamin K-dependent proteins, including clotting factors (II, VII, IX, X) and anticoagulant proteins (protein C and S). It is converted in the body to menadiol, which is active in the carboxylation reaction.

What the body does with it

Metabolism	Primarily hepatic; undergoes reduction to menadiol by microsomal reductase enzymes (e.g., DT-diaphorase). Conjugation with glucuronic acid and sulfate occurs before excretion.
Excretion	Renal: negligible (<1% unchanged); biliary/fecal: >90% as metabolites, primarily menadiol glucuronide and menadione sulfate.
Half-life	Terminal elimination half-life: 2–4 hours in adults with normal hepatic function; prolonged in hepatic impairment or neonates.
Protein binding	~90% bound to albumin; also binds to lipoproteins.
Volume of Distribution	0.6–0.8 L/kg, indicating distribution into extravascular tissues; higher in neonates.
Bioavailability	Oral: ~50% (first-pass metabolism); IM: ~80% (due to incomplete absorption at injection site); IV: 100%.
Onset of Action	Intravenous: within 1–2 hours for prothrombin time correction; intramuscular: within 3–6 hours; oral: within 6–12 hours.
Duration of Action	Prothrombin time correction lasts 12–24 hours after IV; 24–48 hours after IM; 24–72 hours after oral administration. Duration depends on hepatic vitamin K stores and ongoing deficiency.

Classification & Brands

Dosing & administration

5–10 mg intramuscularly or subcutaneously once daily for up to 3 days; oral dose 2–10 mg daily.

Dosage form	TABLET
Renal impairment	No specific adjustment required; use with caution in severe renal impairment (eGFR < 30 mL/min/1.73 m²) due to risk of accumulation.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use due to risk of exacerbating hepatic dysfunction.
Pediatric use	Neonates: 1 mg intramuscularly once; infants and children: 1–5 mg intramuscularly or subcutaneously once daily for 1–3 days.
Geriatric use	No specific dose adjustment; monitor for bleeding or thrombosis due to age-related changes in coagulation. Start at lower end of dosing range (2–5 mg daily).

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MENADIONE (MENADIONE).

Breastfeeding	Menadione is excreted into breast milk; M/P ratio not established. Risk of hemolytic anemia in G6PD-deficient infants. Avoid breastfeeding during therapy or consider temporary discontinuation.
Teratogenic Risk	Menadione (vitamin K3) is contraindicated in pregnancy due to risk of neonatal hemolysis, hyperbilirubinemia, and kernicterus, particularly in third trimester. First trimester exposure may be associated with spontaneous abortion; second and third trimester use may cause fetal distress and premature delivery.

Warnings & precautions

■ FDA Black Box Warning

Menadione has been withdrawn from the U.S. market due to its association with hemolytic anemia, jaundice, and kernicterus in neonates, especially premature infants. It is not FDA-approved for use in newborns.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to menadione or any component","Patients with G6PD deficiency","Newborns, especially premature infants"]

Clinical Precautions

Precautions

["Risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency","Avoid use in neonates due to risk of kernicterus","May cause hypersensitivity reactions including anaphylaxis","Monitor prothrombin time in patients on anticoagulants"]

Clinical Tips & Counseling

Drug interactions

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MENADIONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MENADIONE (MENADIONE).

How it works

What the body does with it

Metabolism	Primarily hepatic; undergoes reduction to menadiol by microsomal reductase enzymes (e.g., DT-diaphorase). Conjugation with glucuronic acid and sulfate occurs before excretion.
Excretion	Renal: negligible (<1% unchanged); biliary/fecal: >90% as metabolites, primarily menadiol glucuronide and menadione sulfate.
Half-life	Terminal elimination half-life: 2–4 hours in adults with normal hepatic function; prolonged in hepatic impairment or neonates.
Protein binding	~90% bound to albumin; also binds to lipoproteins.
Volume of Distribution	0.6–0.8 L/kg, indicating distribution into extravascular tissues; higher in neonates.
Bioavailability	Oral: ~50% (first-pass metabolism); IM: ~80% (due to incomplete absorption at injection site); IV: 100%.
Onset of Action	Intravenous: within 1–2 hours for prothrombin time correction; intramuscular: within 3–6 hours; oral: within 6–12 hours.
Duration of Action	Prothrombin time correction lasts 12–24 hours after IV; 24–48 hours after IM; 24–72 hours after oral administration. Duration depends on hepatic vitamin K stores and ongoing deficiency.

Classification & Brands

Dosing & administration

5–10 mg intramuscularly or subcutaneously once daily for up to 3 days; oral dose 2–10 mg daily.

Dosage form	TABLET
Renal impairment	No specific adjustment required; use with caution in severe renal impairment (eGFR < 30 mL/min/1.73 m²) due to risk of accumulation.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use due to risk of exacerbating hepatic dysfunction.
Pediatric use	Neonates: 1 mg intramuscularly once; infants and children: 1–5 mg intramuscularly or subcutaneously once daily for 1–3 days.
Geriatric use	No specific dose adjustment; monitor for bleeding or thrombosis due to age-related changes in coagulation. Start at lower end of dosing range (2–5 mg daily).

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MENADIONE (MENADIONE).

Breastfeeding	Menadione is excreted into breast milk; M/P ratio not established. Risk of hemolytic anemia in G6PD-deficient infants. Avoid breastfeeding during therapy or consider temporary discontinuation.
Teratogenic Risk	Menadione (vitamin K3) is contraindicated in pregnancy due to risk of neonatal hemolysis, hyperbilirubinemia, and kernicterus, particularly in third trimester. First trimester exposure may be associated with spontaneous abortion; second and third trimester use may cause fetal distress and premature delivery.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to menadione or any component","Patients with G6PD deficiency","Newborns, especially premature infants"]