What is the use and dosage of Mephyton (Vitamin K1) in patients?

Mephyton (Phytonadione/Vitamin K1): Clinical Uses and Dosing

Primary Indications

Mephyton (phytonadione/vitamin K1) is used to reverse vitamin K antagonist (warfarin) anticoagulation and treat vitamin K deficiency-related coagulopathy, with dosing ranging from 1-2.5 mg orally for mild INR elevation to 5-10 mg intravenously for life-threatening bleeding. 1, 2

Dosing by Clinical Scenario

Non-Bleeding Elevated INR

• INR 5.0-9.0 without bleeding: Withhold warfarin; add oral vitamin K1 1-2.5 mg only if patient has increased bleeding risk (advanced age, history of bleeding) 1, 3
• INR >10 without bleeding: Administer oral vitamin K1 3-5 mg in addition to holding warfarin 1, 2
• Oral vitamin K1 reduces INR to <4.0 within 24 hours in 85% of patients 3, 2

Active Bleeding or Emergency Surgery

• Major bleeding: Administer 5-10 mg IV vitamin K1 by slow infusion over 30 minutes 1, 2
• Life-threatening bleeding: Give 10 mg IV vitamin K1 plus 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg IV 4, 1, 2
• Dosing algorithm for PCC based on INR: 25 U/kg if INR 2-4,35 U/kg if INR 4-6, and 50 U/kg if INR >6 4, 1

Hemorrhagic Disease of Newborn

• Prophylaxis: 0.5-1 mg IM within one hour of birth 5
• Treatment: 1 mg subcutaneously or IM; higher doses may be necessary if mother received oral anticoagulants 5

Route of Administration Considerations

Oral administration is strongly preferred for non-emergency situations due to lower risk of adverse reactions compared to IV route. 6 The FDA label states that subcutaneous route should be used whenever possible, and when IV or IM administration is unavoidable, inject very slowly, not exceeding 1 mg per minute 5.

• IV vitamin K1: Acts within 6-12 hours but carries risk of anaphylactoid reactions (3 per 10,000 doses) 4, 7
• Oral vitamin K1: Acts within 18-24 hours, safer profile 8, 6
• Subcutaneous: May cause cutaneous reactions 6

Critical Co-Administration Requirements

Always co-administer vitamin K1 with PCC in life-threatening bleeding because factor VII in PCC has only a 6-hour half-life, requiring vitamin K1 to stimulate endogenous production of vitamin K-dependent factors. 4, 1, 2 Without vitamin K1, the anticoagulation reversal from PCC is temporary and INR will rise again 4.

Important Dosing Caveats

Avoid High-Dose Vitamin K1

• Do not exceed 10 mg vitamin K1, as higher doses create a prothrombotic state and prevent re-warfarinization for days 4, 1, 2
• High-dose vitamin K1 (≥10 mg) causes warfarin resistance for up to one week, requiring heparin bridging if warfarin needs resumption 1, 2
• For mechanical valve patients requiring urgent surgery, use low-dose (1-2 mg) oral vitamin K1 to avoid difficulty achieving therapeutic INR post-procedure 4, 1

Onset of Action

• Minimum 1-2 hours required for measurable improvement in prothrombin time after vitamin K1 administration 5
• Vitamin K1 alone is insufficient for emergent reversal; PCC achieves INR <1.5 within 5-15 minutes versus hours with vitamin K1 alone 1, 2
• IV vitamin K1 acts within 6-12 hours versus 18-24 hours for oral administration 8

Monitoring Requirements

• Recheck INR 30 minutes after PCC administration to assess degree of correction 1
• Monitor INR regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K1 4, 1
• For non-bleeding elevated INR, recheck INR within 24-48 hours after vitamin K1 administration 3

Safety Considerations

Anaphylactoid Reactions

• Occur in 3 per 100,000 IV vitamin K1 doses via non-IgE mechanism, possibly due to solubilizer (polyoxyethylated castor oil) 4, 7
• Can result in cardiac arrest, severe hypotension, bradycardia/tachycardia, dyspnea, and bronchospasm 7
• Reactions occur in patients with and without previous vitamin K1 exposure 7
• Administer IV vitamin K1 by slow infusion over 30 minutes to minimize risk 1, 2, 5

Thrombotic Risk

• PCC use increases risk of venous and arterial thrombosis during recovery period 4
• Thromboprophylaxis must be considered as early as possible after bleeding control 4
• Risk of thromboembolism from overcorrection is in same range as bleeding risk from over-anticoagulation 6

Common Pitfalls

• Administering vitamin K1 unnecessarily for INR <5.0 without bleeding leads to warfarin resistance and difficulty re-establishing therapeutic anticoagulation 3
• Using vitamin K1 alone for life-threatening bleeding without PCC results in inadequate reversal speed 1, 2
• Giving high-dose vitamin K1 (>10 mg) routinely creates prothrombotic state and prolonged warfarin resistance 4, 1, 5
• Expecting immediate coagulant effect when minimum 1-2 hours required for measurable improvement 5
• Using FFP instead of PCC when available: PCC provides more rapid and complete reversal (67% achieve INR ≤1.2 within 3 hours versus 9% with FFP) 1