Vitamin K (Phytonadione) | Medication Reference

Bedside Snapshot

Essential Cofactor: Essential for hepatic synthesis of vitamin K–dependent clotting factors II, VII, IX, X and proteins C/S
Primary Uses: In ICU/ED, used mainly for reversing warfarin effect (elevated INR), and for vitamin K deficiency from malnutrition, cholestasis, or prolonged antibiotics
Route Matters: IV for life-threatening bleeding; oral for non-emergent INR correction; SC is less reliable and generally avoided for warfarin reversal
Delayed Effect: Effect is not immediate; production of new clotting factors takes 6–24 hours, so emergent reversal usually combines vitamin K with PCC or FFP
Warfarin Resistance: Reversing warfarin with high-dose vitamin K may make patients temporarily resistant to re-anticoagulation, important in mechanical valves or high thrombotic risk

Brand & Generic Names

Generic Name: Phytonadione (vitamin K1)
Brand Names: Mephyton (oral), generics

Medication Class

Fat-soluble vitamin; cofactor for clotting factor γ-carboxylation; warfarin reversal agent

Pharmacology

Mechanism of Action:

Acts as an essential cofactor for γ-carboxylation of glutamic acid residues on factors II, VII, IX, X and proteins C/S, enabling calcium binding and full activity
Warfarin inhibits vitamin K epoxide reductase; phytonadione bypasses this by replenishing reduced vitamin K, restoring clotting factor synthesis
In deficiency states, replacement restores hepatic production of functional clotting factors

Pharmacokinetics:

Onset: INR begins to decline within 6–12 hours; maximal effect typically 12–24 hours after administration
Absorption: Oral absorption variable, requires bile salts (fat-soluble); better absorption with food
Distribution: Concentrates in liver; crosses placenta minimally
Metabolism: Hepatic metabolism
Duration: Effects last several days; sufficient to overcome warfarin's anticoagulant effect

Indications

Warfarin reversal: For elevated INR with or without bleeding, depending on severity (see dosing table)
Vitamin K deficiency: From malnutrition, prolonged antibiotic use (disrupts gut flora), cholestatic liver disease, or malabsorption syndromes
Hemorrhagic disease of newborn: Prophylaxis and treatment (pediatric dosing not covered here)
Coagulopathy assessment: Trial in liver disease to distinguish vitamin K deficiency from synthetic failure (though often limited benefit in severe cirrhosis)

Dosing & Administration

Available Forms:

Oral tablets: 5 mg (most common)
IV injection: 1 mg/0.5 mL or 10 mg/mL ampules (must be diluted and infused slowly)
SC/IM injection: available but less preferred for warfarin reversal due to variable absorption

Adult Dosing - Warfarin Reversal:

Scenario	Vitamin K Dose	Route	Notes
Life-threatening bleeding on warfarin (e.g., ICH, massive GI bleed)	5–10 mg	IV	Give with 4-factor PCC (or FFP if PCC unavailable); effect within 6–12h
Serious but non-life-threatening bleeding	2.5–5 mg	IV	Plus PCC or FFP depending on severity and INR
INR ≥10, no significant bleeding	2.5–5 mg	PO	Hold warfarin; recheck INR in 24–48h
INR 4.5–10, no bleeding	0–2.5 mg	PO	Often just hold warfarin; low-dose vitamin K in high-risk patients
Vitamin K deficiency without warfarin	2.5–10 mg	PO/IV	Route per severity; consider malabsorption
Liver disease with coagulopathy	10 mg	IV	Only helpful if actual vitamin K deficiency; often limited benefit in severe cirrhosis

IV Administration: IV phytonadione must be infused slowly (e.g., over ≥30 minutes) to reduce risk of anaphylactoid reactions. Never give IV push.

Contraindications

Contraindications:

Hypersensitivity to phytonadione or formulation components (e.g., some IV preparations contain polyoxyethylated castor oil)

Major Precautions:

IV phytonadione has been associated with rare but serious anaphylactoid reactions; infuse slowly (e.g., over ≥30 minutes)
Reversing warfarin with high-dose vitamin K may make patients temporarily resistant to re-anticoagulation, important in mechanical valves or high thrombotic risk
In liver failure, vitamin K will not correct coagulopathy if the liver cannot synthesize factors; avoid repeated high doses without clear deficiency

Anaphylactoid Risk: Rare but serious reactions with IV administration. Monitor closely during infusion. Infuse slowly over ≥30 minutes.

Warfarin Resistance: High doses can make re-anticoagulation difficult. Use lowest effective dose, especially in patients with mechanical valves or recent VTE.

Adverse Effects

Common:

Pain or irritation at injection site
Flushing or taste disturbances (IV)
Transient resistance to warfarin anticoagulation

Serious (rare):

Anaphylactoid reactions with IV administration (hypotension, bronchospasm, cardiac arrest)
Hemolysis in G6PD deficiency (rare, more with synthetic vitamin K analogs)

Special Populations

Elderly Patients:

No specific dose adjustment required
May be more sensitive to warfarin reversal effects

Renal Impairment:

No dose adjustment required

Hepatic Impairment:

May have reduced clotting factor synthesis even with vitamin K
Trial dose reasonable to assess for deficiency, but limited benefit in severe cirrhosis

Pregnancy:

Category C: Generally considered safe when needed
Crosses placenta minimally

Lactation:

Excreted in breast milk in small amounts
Generally considered compatible with breastfeeding

Monitoring

Clinical Monitoring:

INR before and after vitamin K dosing (usually 12–24h post-dose)
Clinical bleeding vs thrombosis risk, especially in anticoagulated patients with mechanical valves or recent VTE
Signs of hypersensitivity during and shortly after IV administration
Reassess need for re-anticoagulation and appropriate timing

Clinical Pearls

Not Immediate: Vitamin K alone takes 6–24 hours to work. For life-threatening bleeding, always give PCC or FFP along with vitamin K for immediate reversal.

Dosing Strategy: Use the lowest effective dose to avoid warfarin resistance. In patients who need to resume warfarin (mechanical valves), prefer 2.5–5 mg over 10 mg when possible.

Oral vs IV: Oral vitamin K works well for non-emergent INR correction and avoids the anaphylactoid risk of IV. Reserve IV for serious or life-threatening bleeding.

Liver Disease Limitation: In severe cirrhosis, the liver may not be able to synthesize clotting factors even with vitamin K. A trial dose can help distinguish deficiency from synthetic failure, but don't expect miracles.

Slow IV Infusion: Always dilute and infuse IV vitamin K slowly (over ≥30 minutes). Rapid infusion increases anaphylactoid risk.

Recheck INR: INR should be rechecked 12–24 hours after vitamin K administration to assess response and guide further management.

References

1. Lexicomp. (2024). Phytonadione (vitamin K1): Drug information. Wolters Kluwer.
2. Holbrook, A., Schulman, S., Witt, D. M., et al. (2012). Evidence-based management of anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), e152S–e184S. https://doi.org/10.1378/chest.11-2295
3. Dezee, K. J., Shimeall, W. T., Douglas, K. M., et al. (2006). Treatment of excessive anticoagulation with phytonadione (vitamin K): A meta-analysis. Archives of Internal Medicine, 166(4), 391–397. https://doi.org/10.1001/archinte.166.4.391
4. Ageno, W., Gallus, A. S., Wittkowsky, A., et al. (2012). Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), e44S–e88S. https://doi.org/10.1378/chest.11-2292
5. Goldstein, J. N., Refaai, M. A., Milling, T. J., et al. (2015). Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: A phase 3b, open-label, non-inferiority, randomised trial. The Lancet, 385(9982), 2077–2087. https://doi.org/10.1016/S0140-6736(14)61685-8