What is the recommended dose and timing of Vitamin K (phytonadione) administration for a patient with an elevated International Normalized Ratio (INR) of 9.2?

From the Guidelines

For a patient with an elevated INR of 9.2, the recommended dose of Vitamin K (phytonadione) is 2.5-5 mg orally, as stated in the most recent guidelines 1. This dose should be administered as soon as possible, with INR rechecked in 24-48 hours to assess response. The oral route is preferred for non-bleeding patients due to the lower risk of adverse reactions, as noted in previous studies 1. If the patient is actively bleeding or requires urgent reversal, 5-10 mg of Vitamin K should be given intravenously (IV) instead, with a slow infusion rate over 20-30 minutes to avoid anaphylactoid reactions. Vitamin K works by promoting the hepatic synthesis of clotting factors II, VII, IX, and X, which are inhibited by warfarin. The effect begins within 6-12 hours for oral administration and 1-2 hours for IV administration. Patients should temporarily hold their warfarin dose and be monitored closely until the INR returns to the therapeutic range. For very high INRs like 9.2, prothrombin complex concentrate or fresh frozen plasma may also be considered if there is significant bleeding or high bleeding risk, as suggested by recent guidelines 1.

Some key points to consider when administering Vitamin K include:

• The dose and route of administration depend on the severity of the INR elevation and the presence of bleeding or high bleeding risk.
• Oral Vitamin K is preferred for non-bleeding patients, while IV administration is reserved for urgent reversal or significant bleeding.
• The effect of Vitamin K begins within 6-12 hours for oral administration and 1-2 hours for IV administration.
• Patients should be monitored closely until the INR returns to the therapeutic range, and warfarin dose adjustments should be made as needed. The most recent study 1 provides the best guidance on the management of elevated INR, and its recommendations should be followed in clinical practice.

From the FDA Drug Label

The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2.5 mg to 10 mg or up to 25 mg initially. In some instances 50 mg may be required. Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based upon the INR or clinical condition.

For an INR of 9.2, the recommended dose of Vitamin K (phytonadione) is 2.5 mg to 10 mg or up to 25 mg initially. The dose may be repeated if the INR remains prolonged after 6 to 8 hours, with subsequent dosage modified based on the INR or clinical condition. In some instances, a dose of up to 50 mg may be required 2.

From the Research

Vitamin K Administration for Elevated INR

The administration of Vitamin K (phytonadione) is a common approach to reverse elevated International Normalized Ratio (INR) levels, which can be life-threatening. For a patient with an INR of 9.2, the following considerations are important:

• Dose and Timing: The dose of Vitamin K can vary based on the severity of the INR elevation and the clinical context. However, the provided studies do not specify a particular dose for an INR of 9.2 3, 4, 5, 6, 7.
• Reversal Strategies: Several strategies can be employed for rapid warfarin reversal, including the use of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and recombinant activated factor VII 4, 5, 6.
• Effectiveness and Safety: The effectiveness and safety of these strategies can vary. For example, PCC has been shown to be effective for rapid INR reversal and effective haemostasis in patients needing urgent surgical or invasive procedures 3.
• Considerations for Kidney Function: Patients with lower estimated glomerular filtration rate (eGFR) may experience slower anticoagulation reversal and have a higher risk of hemorrhage at INR ≥ 4 7.

Key Points for Vitamin K Administration

• Vitamin K (phytonadione) is used to reverse elevated INR levels.
• The dose and timing of Vitamin K administration may depend on the clinical context and severity of INR elevation.
• Several reversal strategies are available, including FFP, PCC, and recombinant activated factor VII.
• Kidney function should be considered when managing anticoagulation reversal.

Reversal Strategies

• FFP: Can be used for warfarin reversal, but may have a slower onset of action compared to PCC or recombinant activated factor VII 4, 5.
• PCC: Has been shown to be effective for rapid INR reversal and effective haemostasis in patients needing urgent surgical or invasive procedures 3, 5.
• Recombinant Activated Factor VII: May be used as an adjunct to Vitamin K for rapid warfarin reversal, but is more expensive and may have a greater risk of INR rebound 4.