Phytomenadione

Why this drug is interesting

Vitamin K is the only part of warfarin reversal that reverses anything. Prothrombin complex concentrate replaces the missing factors; fresh frozen plasma replaces fewer of them more slowly. Neither does anything about the reason the factors are missing, which is that warfarin is still inhibiting vitamin K epoxide reductase and the liver still cannot γ-carboxylate.

It is also the drug that most often gets left out. It is cheap, it is slow, it does not feel like an intervention, and by the time it matters the patient has left the department. The predictable consequence — a patient whose INR was normal at midnight and is 6 again at breakfast — is one of the more avoidable events in acute medicine.

Pharmacology

Mechanism

Phytomenadione is vitamin K₁. It is the cofactor for the γ-carboxylation of glutamate residues on factors II, VII, IX and X, and on proteins C and S — the modification that allows these factors to bind calcium and assemble on phospholipid membranes. Warfarin blocks the recycling of vitamin K epoxide back to the active quinol; supplying exogenous vitamin K overcomes the block by mass action.

Because the mechanism requires the liver to synthesise new, properly carboxylated factors, the effect is inevitably delayed. There is no formulation and no route that changes this.

The mixed micelle formulation

Konakion MM uses glycocholic acid and lecithin to form mixed micelles rather than a polyethoxylated castor oil vehicle. The SmPC attributes its intravenous tolerability to the "absence of organic solvents". It is a genuine improvement on older preparations, but it has not abolished the anaphylactoid risk — see below.

Route — and why intramuscular is prohibited

Administration

• Slow intravenous injection over at least 30 seconds
• For infusion, dilute with 55 mL of 5% glucose; prepare freshly and protect from light
• Do not dilute or mix with other injectables — it may be injected into the lower part of a running infusion set
• For small doses, one or more ampoules of Konakion MM Paediatric 2 mg/0.2 mL (the same solution) can be used — a much easier way to give 0.5 or 1 mg accurately than trying to draw a fraction of the 10 mg ampoule

Dosing

The licensed indication is "as an antidote to anticoagulant drugs of the coumarin type in the treatment of haemorrhage or threatened haemorrhage, associated with a low blood level of prothrombin or factor VII."¹

Adults — major and life-threatening bleeding

• Withdraw the coumarin anticoagulant
• Recheck the INR at 3 hours and repeat the dose if the response has been inadequate
• Maximum 40 mg intravenously in 24 hours
• Monitor coagulation profiles daily until acceptable, and more frequently in severe cases

Adults — asymptomatic high INR

The label emphasises that treatment of the asymptomatic patient depends on the indication for anticoagulation, the INR value, how long it has been out of range, patient factors and the associated bleeding risk — and that these figures are "provided for therapeutic guidance only."¹ The doses are deliberately small: enough to bring the INR down, not enough to make the patient resistant to re-anticoagulation.

Reversal before surgery

"Patients who require emergency surgery that can be delayed for 6-12 hours can be given 5 mg intravenous vitamin K₁ to reverse the anticoagulant effect. If surgery cannot be delayed, PCC can be given in addition to intravenous vitamin K₁ and the INR checked before surgery."¹

Children aged 1–18 years

• Major or life-threatening bleeding: 5 mg IV is suggested, with PCC if appropriate (or FFP if PCC unavailable)
• Asymptomatic high INR (>8) in a clinically well child: 30 micrograms/kg IV has been reported to be effective
• Recheck the INR at 2–6 hours and repeat if the response is inadequate
• There are no dose-ranging studies in children with haemorrhage — the label describes these as suggestions based on clinical experience, and advises consulting a haematologist
• Bear in mind that vitamin K administration is "likely to interfere with anticoagulation with warfarin for 2-3 weeks" — a substantial consideration in a child with a mechanical valve

Anticoagulants other than warfarin

The doses above apply to warfarin. The label notes limited data for acenocoumarol and phenprocoumon, whose different half-lives may require different vitamin K doses. Vitamin K has no role in reversing direct oral anticoagulants — apixaban, rivaroxaban, edoxaban and dabigatran do not act through vitamin K metabolism. See andexanet alfa.

Other indications

Vitamin K deficiency bleeding of the newborn

Prophylaxis against haemorrhagic disease of the newborn is given with Konakion MM Paediatric 2 mg/0.2 mL, a separate product with its own SmPC and its own dosing schedules for intramuscular and oral routes. Follow local neonatal policy — this is not the adult 10 mg/mL preparation and the routes are not interchangeable.

Other causes of vitamin K deficiency

The label lists likely paediatric indications that generalise to adults: conditions interfering with absorption (chronic diarrhoea, cystic fibrosis, biliary atresia, hepatitis, coeliac disease), poor nutrition with broad-spectrum antibiotic exposure, and liver disease. In liver disease the coagulopathy is usually synthetic rather than a vitamin K deficiency, and a trial of vitamin K corrects only the deficient component — an important distinction, since a prolonged INR in cirrhosis does not mean the patient is auto-anticoagulated.

Superwarfarin poisoning

Long-acting anticoagulant rodenticides — brodifacoum, difenacoum — produce vitamin K antagonism lasting weeks to months, and require high-dose oral vitamin K for a prolonged period. This is a specialist problem: discuss with the National Poisons Information Service and consult TOXBASE.

Adverse effects

• Anaphylactoid reactions after intravenous injection
• Venous irritation or phlebitis — very rare
• Warfarin resistance for days to weeks after large doses; the label warns of 2–3 weeks' interference in children
• Injection-site haematoma if the intramuscular route is used in an anticoagulated patient

Contraindications

Known hypersensitivity to any of the constituents. That is the entire list — the barrier to giving vitamin K is very low, which is another reason its omission is hard to justify.

Practical use in the ED

1. Prescribe it with the PCC, in the same decision. The two belong together, and separating them in time is how the second gets forgotten.
2. Pick the dose from the bleeding, not the INR alone. A bleeding patient gets 5–10 mg; an asymptomatic patient with an INR of 12 gets 1 mg. Giving the bleeding dose to the asymptomatic patient makes them difficult to re-anticoagulate for weeks.
3. Use the paediatric ampoule for small doses. 0.5 mg out of a 10 mg/mL ampoule is a dilution error waiting to happen; 2 mg/0.2 mL is the same solution and much easier.
4. Give it slowly and watch. At least 30 seconds, and stay for it.
5. Recheck the INR at 3 hours after a bleeding dose, and repeat if the response is inadequate — up to 40 mg in 24 hours.
6. Ask why the INR was high. Missed dose adjustment, a new antibiotic, intercurrent illness, deliberate overdose, poor nutrition. Reversing the number without answering that returns the patient to you.

Critical appraisal

1. The dose thresholds for asymptomatic high INR are consensus, and consensus has shifted. Earlier guidance was more interventionist about high INRs without bleeding; the evidence since has consistently shown that most asymptomatic patients do not bleed and that omitting warfarin with or without a small vitamin K dose is usually sufficient. Randomised evidence for giving vitamin K to an asymptomatic patient with an INR of 6 shows little benefit and real harm from over-correction.
2. The intravenous versus oral question for non-bleeding patients is not fully settled. Oral vitamin K is effective, avoids the anaphylactoid risk entirely, and works over a similar timescale for a non-urgent correction. UK labels and guidelines lean intravenous for the acute setting, and that is a reasonable default in the emergency department — but for the well patient with an incidental high INR, oral is a legitimate option and the reflex to cannulate deserves questioning.
3. The anaphylactoid risk is quoted with more confidence than the data support. Reported rates come from spontaneous reporting and older formulations; the true incidence with the current mixed micelle product in current practice is not well characterised. It is almost certainly low, and it has been used to justify withholding vitamin K from bleeding patients, which is a clear error in the other direction.
4. The omission problem is not a knowledge problem. Almost every clinician who gives PCC knows vitamin K should accompany it. The failure happens in prescribing systems, handovers and the gap between the emergency and the ward. Order sets that pair the two are more effective than any amount of teaching.

References

1. 1
   Konakion MM 10 mg/ml solution for injection — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.4, 4.8, 5.2. Source of all doses, the intramuscular prohibition, the 40 mg ceiling and the 4–6 hour onset. Verified 23 Aug 2026.
2. 2
   Konakion MM Paediatric 2 mg/0.2 ml solution for injection — Summary of Product Characteristics. electronic Medicines Compendium. The preparation to use for small adult doses and for neonatal prophylaxis; different dosing schedules apply to the latter.
3. 3
   Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin — fourth edition. British Committee for Standards in Haematology. Br J Haematol 2011;154(3):311–24. PubMed
4. 4
   Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med 2009;150(5):293–300. PubMed The evidence behind restraint in the asymptomatic high INR.
5. 5
   TOXBASE — anticoagulant rodenticides (superwarfarins); vitamin K. National Poisons Information Service. toxbase.org (NHS login required. NPIS: 0344 892 0111.)
6. 6
   Phytomenadione — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk