Phytomenadione

Vitamin K1. Haemostatics. Antagonist of indirect anticoagulants

ATC code: B02BA01 (Phytomenadione (vitamin K1))

Brand names

Phytonadione USP, Konakion MM, Mephyton

Mechanism of action

Vitamin K1 (phylloquinone) is a cofactor for hepatic γ-glutamyl carboxylase, which activates clotting factors II (prothrombin), VII, IX, X, and the natural anticoagulants proteins C, S, Z. Without vitamin K, the liver synthesises inactive precursors of these factors, manifesting as prolonged prothrombin time and bleeding. The intramuscular effect develops within 4–6 hours, intravenous within 1–2 hours. After oral intake, coagulation parameters normalise over 12–24 hours. Vitamin K1 is fundamentally different from vitamin K3 (menadione sodium bisulfite, Vikasol): K3 acts more slowly and weakly, and in neonates causes haemolytic anaemia and kernicterus. International practice does not use K3 for VKDB or anticoagulant reversal – only K1.

Indications

Coagulopathy in cholestasis and malabsorption

First line

Vitamin K1 is first-line for vitamin K-deficient coagulopathy in cholestatic liver disease, malabsorption syndromes (cystic fibrosis, coeliac disease, short bowel syndrome), and long-term parenteral nutrition. Doses: 5–10 mg IM or subcutaneously daily for 3 days, then guided by INR. In children with cholestasis: 1–2 mg/kg. In patients with severe coagulopathy and bleeding: 10 mg slow IV with concurrent PCC or FFP transfusion.

Sources

ACCP: Evidence-Based Management of Anticoagulant Therapy: ACCP 9th Edition (2012)

Reversal of warfarin anticoagulant effect

First line

First-line agent for reversing excessive warfarin anticoagulation per ACCP recommendations. Dose and route depend on the situation. INR 4.5–10 without bleeding: hold 1–2 warfarin doses without vitamin K or 1–2.5 mg oral. INR above 10 without bleeding: 2.5–5 mg oral. Any significant warfarin-associated bleeding: 5–10 mg slow intravenous (over 30 minutes – rapid administration causes anaphylactoid reactions) plus prothrombin complex concentrate (4F-PCC) or fresh frozen plasma. The intravenous effect develops over 1–2 hours, oral over 12–24 hours. Vikasol (K3) is not used for this purpose – it acts more slowly and weakly.

Sources

Vitamin K deficiency bleeding (VKDB) prevention in newborns

First line

Global paediatric standard: vitamin K1 1 mg intramuscularly once within the first 6 hours of life for term newborns; 0.4 mg/kg for preterm under 1,500 g, 0.5–1 mg for preterm above 1,500 g. AAP, NICE NG194, and WHO 2022 unanimously recommend the intramuscular route. Alternative oral regimens (3 doses of 2 mg on days 1, 4–7, and 28) are acceptable when parents refuse injection, but efficacy is lower: late VKDB rate is 1.2–6.4 per 100,000 live births with oral regimens versus 0.25 per 100,000 after IM. Without prophylaxis, late VKDB causes intracranial haemorrhage with up to 20 % mortality and severe disability. K1 (phytomenadione) is used for this purpose, not K3 (Vikasol) – K3 causes haemolytic anaemia in neonates.

Sources

Anti-aging and longevity (marketed indication)

Not recommended

International guidelines do not list vitamin K1 as an anti-ageing agent. Supplement marketing sometimes positions phytomenadione as a «vitamin for vessels and bones», borrowing the K2 narrative. K1 has not shown a systemic effect on bone mineral density or vascular calcification in RCTs – that activity belongs to K2-dependent tissue Gla proteins (osteocalcin, matrix Gla protein). K1 above dietary intake provides no clinical benefit in healthy individuals.

Sources

Cochrane: Prophylactic vitamin K for vitamin K deficiency bleeding in neonates (2000)

Practical notes

Timing and administration

Newborn: intramuscular injection of 1 mg into the antero-lateral thigh within the first 6 hours of life. Adults for warfarin reversal: oral or slow intravenous (over 30 minutes). Faster IV administration is associated with anaphylactoid reactions and cardiac arrest. Subcutaneous administration in adults is an acceptable alternative with slower onset.

Monitoring

After warfarin reversal, INR is checked at 6, 12, and 24 hours post-K1. After standard newborn prophylaxis, no specific monitoring is required. In cholestasis- or malabsorption-related coagulopathy, INR is monitored every 1–3 days until stable, then clinically.

Special situations

In warfarin patients requiring rapid re-anticoagulation (mechanical heart valve, recent VTE), high-dose K1 hinders warfarin re-saturation for 1–2 weeks. In such cases, the minimum effective K1 dose is used, with PCC or FFP for immediate INR correction. In G6PD deficiency, high-dose intravenous K1 may cause haemolysis.

Common myths

Vitamin K1 for newborns and vitamin K in supplements are different products with different evidence bases. Common misconceptions include the following.

Myth: «the vitamin K shot at birth is unnecessary, you can refuse or use drops». Fact: intramuscular K1 1 mg in the first hours of life is the unanimous recommendation of AAP, NICE, WHO, and Russian normal-pregnancy guidelines. Without prophylaxis, the late VKDB risk with intracranial haemorrhage is 4–7 per 100,000 live births. Oral regimens are acceptable when injection is refused but are less effective.

Myth: «Vikasol can be given to an infant instead of K1». Fact: Vikasol is K3 (menadione sodium bisulfite), a synthetic molecule. In newborns, K3 causes haemolytic anaemia and kernicterus risk. AAP, ESPGHAN, and NICE explicitly state that only K1 (phytomenadione) is used for VKDB. International paediatric practice has not used K3 for decades. Russian package inserts still list Vikasol as a «vitamin K» drug – this is outdated practice.

Myth: «vitamin K at birth is linked to childhood leukaemia». Fact: this hypothesis came from a single Golding et al. 1992 paper. Subsequent large epidemiological studies (Roman 2002, Fear 2003, McKinney 2003) did not confirm the association. AAP in its position statement explicitly rejects the hypothesis. Refusing K1 prophylaxis based on this myth raises real VKDB risk.

Myth: «K1 and K2 are interchangeable – they are just vitamins K». Fact: different molecules, different target tissues, different indications. K1 (phytomenadione) acts on hepatic clotting factors – the only form for VKDB and warfarin reversal. K2 (menaquinone) acts on tissue Gla proteins – marketed for bones and vessels with weak clinical basis. They do not substitute for each other across indications.

Myth: «extra K1 in adults improves clotting». Fact: in a healthy adult, vitamin K is not deficient and clotting factors synthesise normally. Supplemental K1 without a clinical indication has no effect. In patients on warfarin, supplemental K1 is dangerous – it disrupts anticoagulation.

Safety

Contraindications

Hypersensitivity to phytomenadione
Severe hepatic failure with markedly reduced synthetic function (K1 effect is minimal)

Serious adverse effects

Anaphylactoid reactions on rapid intravenous administration – cardiac arrest, severe bronchospasm, hypotension. Strict requirement: IV administration slower than 30 minutes, diluted in normal saline or 5 % dextrose
Haemolytic anaemia and kernicterus in newborns when menadione (K3, Vikasol) is used instead of phytomenadione (K1) – the reason K3 was removed from international paediatric practice

Common adverse effects

Injection-site pain and erythema
Facial flushing, sensation of warmth (after intravenous administration)

Uncommon adverse effects

Allergic reactions (rash, pruritus)
Altered taste

PregnancyFDA C

FDA category C. Used in pregnancy for anticoagulant- or deficiency-related coagulopathy. Phytomenadione transfers across the placenta poorly, so newborn prophylaxis via maternal third-trimester intake is less effective than post-delivery injection of the infant.

Breastfeeding

Breast milk contains little vitamin K (1–4 µg/L), so maternal K1 intake is insufficient to prevent VKDB in the infant. Standard practice: direct K1 injection to the newborn. Maternal K1 intake is compatible with breastfeeding.