Injectable Vitamin K (Phytonadione): Indications, Dosing, and Contraindications
Newborn Prophylaxis and Treatment
For prevention of hemorrhagic disease of the newborn, administer phytonadione 0.5–1 mg intramuscularly within one hour of birth as a single dose. 1
- The intramuscular route is strongly preferred over oral administration because it provides superior efficacy against early, classic, and late vitamin K deficiency bleeding (VKDB). 2
- For treatment of established hemorrhagic disease in newborns, give phytonadione 1 mg subcutaneously or intramuscularly; higher doses may be necessary if the mother received oral anticoagulants. 1
- A prompt response (shortening of prothrombin time within 2–4 hours) following vitamin K administration is diagnostic of hemorrhagic disease of the newborn; failure to respond indicates another coagulation disorder. 1
Warfarin Reversal in Adults: Algorithm by Clinical Scenario
Life-Threatening Bleeding (Any INR)
Immediately administer 4-factor prothrombin complex concentrate (PCC) 25–50 U/kg IV plus vitamin K 5–10 mg by slow IV infusion over 30 minutes, targeting INR <1.5. 3, 4, 5
PCC dosing algorithm based on INR: 3, 4
- INR 2 to <4: 25 U/kg
- INR 4–6: 35 U/kg
- INR >6: 50 U/kg
PCC achieves INR correction within 5–15 minutes, whereas vitamin K alone requires 4–6 hours; therefore, never rely on vitamin K monotherapy for major bleeding. 3, 4
Vitamin K must be co-administered because factor VII in PCC has a half-life of only 6 hours, requiring vitamin K to stimulate endogenous synthesis of clotting factors. 3, 4, 5
Recheck INR 15–60 minutes after PCC administration to assess correction. 4, 5
Major Non-Life-Threatening Bleeding
Administer vitamin K 5–10 mg IV by slow infusion over 30 minutes; add PCC if bleeding occurs at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal) or if the patient is hemodynamically unstable. 3, 4, 5
- For minor bleeding with INR elevation, stop warfarin and give vitamin K 5–10 mg IV. 5
Emergency Surgery Requiring Rapid Reversal
Administer 4-factor PCC 25–50 U/kg IV plus vitamin K 5–10 mg by slow IV infusion over 30 minutes, targeting INR <1.5. 3, 5
- This combination achieves surgical hemostasis within 15 minutes compared to hours with fresh frozen plasma. 3
INR >10 Without Bleeding
Immediately stop warfarin and give oral vitamin K 2.5–5 mg; repeat INR within 24 hours. 3, 4, 5
- Oral administration is preferred for non-emergency situations due to lower risk of anaphylactoid reactions (3 per 100,000 IV doses). 3, 4
- The risk of spontaneous major bleeding is 3.9% at 90 days when INR >10. 3
INR 5.0–9.0 Without Bleeding
Withhold warfarin for 1–2 doses and monitor serial INR determinations; do NOT routinely administer vitamin K. 3, 5
- Add oral vitamin K 1–2.5 mg only if high bleeding risk factors exist: age >65–75 years, history of bleeding, concomitant antiplatelet drugs, renal failure, or alcohol use. 3, 5
- Randomized trials show vitamin K accelerates INR normalization but does not reduce major bleeding rates (2% with vitamin K vs 0.8% without). 3, 5
INR 4.5–5.0 Without Bleeding
Withhold warfarin completely until INR falls back into therapeutic range (typically 24–72 hours), then restart at a reduced weekly dose of 10–20% less than the previous dose. 3, 5
Route Selection and Administration Technique
Intravenous administration is the preferred route for rapid warfarin reversal because it achieves predictable INR reduction within 4–6 hours, compared with 18–24 hours for oral dosing and unpredictable results with subcutaneous injection. 3, 6
- Dilute phytonadione in 25–50 mL of preservative-free 0.9% sodium chloride, 5% dextrose, or a combination of both. 3, 1
- Infuse slowly over 15–30 minutes, never exceeding 1 mg per minute, to minimize adverse reactions. 3, 4, 1
- Subcutaneous administration yields an unpredictable pharmacologic response and is therefore not recommended for urgent warfarin reversal. 3, 6
- In a prospective randomized trial, mean INR at 8 hours was 4.6 in the IV group versus 8.0 in the SC group (P = 0.006), demonstrating superior efficacy of the IV route. 6
Dosing Limits and Safety Considerations
Never exceed 10 mg of vitamin K in most clinical scenarios; doses above this threshold increase thrombotic risk and cause warfarin resistance lasting up to one week. 3, 4, 5
- High-dose vitamin K may require heparin bridging when warfarin needs to be resumed. 3
- Anaphylactic reactions to IV vitamin K occur at a rate of approximately 3 per 100,000 doses via a non-IgE mechanism, attributed to the polyoxyethylated castor oil solubilizer, presenting with cardiac arrest, severe hypotension, arrhythmias, dyspnea, and bronchospasm. 3, 4, 5
- Avoid rapid IV push of vitamin K; this method dramatically increases the risk of anaphylaxis. 4
Thrombosis Risk and Monitoring
PCC use is associated with increased risk of both venous and arterial thrombosis during the recovery period; initiate thromboprophylaxis as early as feasible after bleeding control. 4, 5
- Monitor INR regularly over the next week, as a minority of patients require more than one week to clear warfarin and may need additional vitamin K. 4, 5
- Three-factor PCC carries higher thrombotic risk than 4-factor PCC in trauma patients. 5
Special Populations and Considerations
Mechanical Heart Valves
For patients with mechanical prosthetic valves and supratherapeutic INR requiring urgent surgery, use low-dose (1–2 mg) oral vitamin K to avoid difficulty achieving therapeutic INR post-procedure. 3, 5
- Caution is needed with vitamin K administration to avoid valve thrombosis if INR falls too rapidly. 3, 5
- Higher doses of vitamin K are discouraged to prevent prolonged warfarin resistance. 5
Patients with Anaphylaxis History
In patients with a history of anaphylaxis, intravenous vitamin K is absolutely contraindicated regardless of INR level or bleeding status; oral administration is the only safe route even in urgent situations. 5
- For major bleeding in these patients, administer 4-factor PCC 25–50 U/kg IV plus oral vitamin K 5–10 mg simultaneously. 5
Oral Administration of Injectable Formulation
Injectable vitamin K can be administered orally when tablets are unavailable or cost-prohibitive; this route is effective and safe. 7, 8
- In a retrospective study of 200 patients, IV phytonadione solution given orally performed similarly to tablets for warfarin reversal (INR <1.5 at 24 hours, p = 0.321). 8
- Injectable vitamin K for oral administration can be prepared as an undiluted solution or as a compounded solution. 7
Common Pitfalls to Avoid
- Do not rely on vitamin K monotherapy for major bleeding; always pair it with 4-factor PCC for rapid hemostatic correction. 3, 4
- Avoid the subcutaneous route for urgent reversal because of unreliable absorption and delayed response. 3, 6
- Do not use subcutaneous vitamin K for a 10 mg dose; the FDA label recommends IV or IM administration. 4
- Administering vitamin K intravenously when not necessary can lead to anaphylactic reactions. 3
- Giving excessive doses of vitamin K can lead to warfarin resistance and prothrombotic state. 3, 4
- Failing to identify and address the underlying cause of elevated INR (drug interactions, dietary changes, illness) can lead to recurrence. 3, 5