KONAKION

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KONAKION (KONAKION).

How it works

Phytonadione (vitamin K1) is a fat-soluble vitamin that serves as a cofactor for the hepatic microsomal enzyme vitamin K epoxide reductase, which is responsible for the post-translational carboxylation of glutamic acid residues (Gla residues) on clotting factors II, VII, IX, and X, as well as proteins C and S. Carboxylation allows these factors to bind calcium and phospholipids, enabling their activation in the coagulation cascade.

What the body does with it

Metabolism	Phytonadione is rapidly metabolized in the liver via side-chain oxidation and reduction, followed by conjugation with glucuronic acid and biliary excretion. The major metabolic pathway involves the side-chain oxidation to phylloquinone oxide, which is then reduced back to phytonadione by vitamin K epoxide reductase.
Excretion	Primarily fecal via bile (60-70%) and renal (10-20%) as metabolites; unchanged drug excretion is minimal.
Half-life	Terminal elimination half-life is 1.5-2.5 hours for phytonadione; clinical effect on INR persists for 24-48 hours.
Protein binding	Highly protein bound (>99%), primarily to lipoproteins; minimal binding to albumin.
Volume of Distribution	0.3 L/kg; distributes to liver and other tissues with high drug concentration at site of action.
Bioavailability	Oral: 50-80% (saturable absorption); IM: approximately 100%; IV: 100%.
Onset of Action	IV: 1-2 hours for INR reduction; IM: 3-6 hours; Oral: 6-10 hours; Subcutaneous: variable (avoid due to hematoma risk).
Duration of Action	INR reversal lasts 12-48 hours depending on dose and severity; may require repeat dosing for long-acting anticoagulants.

Classification & Brands

Dosing & administration

1-10 mg IM or subcutaneously (slow IV infusion over 15-30 min if necessary) once; for warfarin reversal, dose based on INR: 1-2.5 mg PO if INR >5, 2.5-5 mg if INR >9, or 10 mg IV if major bleeding.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No specific guidelines; use with caution in severe hepatic impairment as vitamin K may not correct coagulopathy due to synthetic dysfunction.
Pediatric use	Newborns: 0.5-1 mg IM once at birth (prophylaxis). Children: 0.5-5 mg IM/IV once depending on indication and weight (typically 0.03 mg/kg/day for deficiency).
Geriatric use	No specific dose adjustment; use lowest effective dose due to potential increased sensitivity to reversal agents.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KONAKION (KONAKION).

Breastfeeding	Phytonadione is excreted into breast milk in low amounts. The M/P ratio is not well established but is considered low. It is considered compatible with breastfeeding. Supplementation to the infant is not required except for specific neonatal indications.
Teratogenic Risk	Phytonadione (vitamin K1) is not teratogenic. No increased risk of congenital anomalies has been observed. However, administration of phytonadione to pregnant women at term may be used to prevent hemorrhagic disease of the newborn. Use in first trimester is not associated with fetal harm.

Warnings & precautions

■ FDA Black Box Warning

Intravenous administration of phytonadione has been associated with severe reactions, including anaphylaxis, cardiorespiratory arrest, and death. Intravenous use should be reserved for emergency situations when the benefits outweigh the risks, and appropriate resuscitation equipment should be available.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to phytonadione or any component of the formulation","Intravenous administration is contraindicated in neonates due to risk of benzyl alcohol toxicity (if formulation contains benzyl alcohol)","Not recommended for treatment of hemophilia A or B, von Willebrand disease, or other coagulopathies unrelated to vitamin K deficiency"]

Clinical Precautions

Precautions

["Intravenous administration: Risk of severe anaphylactoid reactions; intravenous route should only be used when absolutely necessary and with close monitoring.","Neonates: Use with caution in neonates, especially those with hyperbilirubinemia, as vitamin K may increase the risk of kernicterus (though this is rare with current formulations).","Patients with liver disease: May be less effective in severe hepatic impairment due to inability to synthesize clotting factors.","Laboratory monitoring: Prothrombin time (PT/INR) should be monitored to assess response."]

Clinical Tips & Counseling

Drug interactions

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KONAKION

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KONAKION (KONAKION).

How it works

What the body does with it

Metabolism	Phytonadione is rapidly metabolized in the liver via side-chain oxidation and reduction, followed by conjugation with glucuronic acid and biliary excretion. The major metabolic pathway involves the side-chain oxidation to phylloquinone oxide, which is then reduced back to phytonadione by vitamin K epoxide reductase.
Excretion	Primarily fecal via bile (60-70%) and renal (10-20%) as metabolites; unchanged drug excretion is minimal.
Half-life	Terminal elimination half-life is 1.5-2.5 hours for phytonadione; clinical effect on INR persists for 24-48 hours.
Protein binding	Highly protein bound (>99%), primarily to lipoproteins; minimal binding to albumin.
Volume of Distribution	0.3 L/kg; distributes to liver and other tissues with high drug concentration at site of action.
Bioavailability	Oral: 50-80% (saturable absorption); IM: approximately 100%; IV: 100%.
Onset of Action	IV: 1-2 hours for INR reduction; IM: 3-6 hours; Oral: 6-10 hours; Subcutaneous: variable (avoid due to hematoma risk).
Duration of Action	INR reversal lasts 12-48 hours depending on dose and severity; may require repeat dosing for long-acting anticoagulants.

Classification & Brands

Dosing & administration

1-10 mg IM or subcutaneously (slow IV infusion over 15-30 min if necessary) once; for warfarin reversal, dose based on INR: 1-2.5 mg PO if INR >5, 2.5-5 mg if INR >9, or 10 mg IV if major bleeding.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No specific guidelines; use with caution in severe hepatic impairment as vitamin K may not correct coagulopathy due to synthetic dysfunction.
Pediatric use	Newborns: 0.5-1 mg IM once at birth (prophylaxis). Children: 0.5-5 mg IM/IV once depending on indication and weight (typically 0.03 mg/kg/day for deficiency).
Geriatric use	No specific dose adjustment; use lowest effective dose due to potential increased sensitivity to reversal agents.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KONAKION (KONAKION).

Breastfeeding	Phytonadione is excreted into breast milk in low amounts. The M/P ratio is not well established but is considered low. It is considered compatible with breastfeeding. Supplementation to the infant is not required except for specific neonatal indications.
Teratogenic Risk	Phytonadione (vitamin K1) is not teratogenic. No increased risk of congenital anomalies has been observed. However, administration of phytonadione to pregnant women at term may be used to prevent hemorrhagic disease of the newborn. Use in first trimester is not associated with fetal harm.