What is the recommended method for administering vitamin K (Vitamin K1, phylloquinone)?

How to Administer Vitamin K

Vitamin K1 (phylloquinone) should be administered via the subcutaneous or oral route whenever possible, with intravenous administration reserved only when unavoidable and given by slow injection not exceeding 1 mg per minute to minimize the risk of anaphylactoid reactions. 1

Route Selection and Safety Considerations

Preferred Routes of Administration

• Subcutaneous administration is the preferred parenteral route when oral administration is not feasible 1
• Oral administration is effective and safe for most supplementation needs, with absorption occurring within 24 hours 2
• Intramuscular administration is specifically recommended for newborn prophylaxis (0.5-1.0 mg within one hour of birth) 2, 1

Intravenous Administration: Use with Extreme Caution

• IV administration should only be used when subcutaneous or oral routes are unavoidable 1
• Maximum infusion rate: 1 mg per minute to reduce risk of severe reactions 1
• Anaphylactoid reactions occur in approximately 3 per 100,000 IV doses, potentially causing bronchospasm and cardiac arrest 3, 2
• Maximum effect occurs within 6-12 hours after IV administration 2

Critical Dosing Limits

• Never exceed 10 mg per dose in acute settings, as higher doses can create a prothrombotic state and prevent re-anticoagulation for days 3

Dosing by Clinical Indication

Newborn Prophylaxis

• 0.5-1.0 mg intramuscularly within one hour of birth for all healthy newborns 2, 1
• Higher doses may be necessary if the mother has been receiving oral anticoagulants 1

Hemorrhagic Disease of the Newborn (Treatment)

• 1 mg subcutaneously or intramuscularly as initial treatment 1
• Response should occur within 2-4 hours; failure to respond indicates another diagnosis 1

Anticoagulant Reversal in Adults

• 2.5-10 mg initially for excessively prolonged prothrombin time from oral anticoagulants 1
• Up to 25 mg may be used in standard cases; rarely 50 mg may be required 1
• For life-threatening VKA-associated bleeding: 10 mg IV by slow injection along with four-factor prothrombin complex concentrate 3
• Reassess in 6-8 hours; repeat dose if prothrombin time not adequately shortened 1

Hypoprothrombinemia from Other Causes

• 2.5-25 mg (rarely up to 50 mg) depending on severity and response 1

Chronic Supplementation

For Cystic Fibrosis:

• Infants: 0.3-1.0 mg/day orally 4, 2
• Older children and adults: 1-10 mg/day orally depending on age and risk factors 4, 2
• Daily administration is essential due to low storage capacity of vitamin K 4, 2

For Parenteral Nutrition:

• Preterm infants: 10 μg/kg/day 2
• Adults: 200 μg/day (typically provided through lipid emulsions and multivitamin preparations) 2
• Weekly IV supply of 250-500 μg from lipids is sufficient to restore and maintain normal plasma levels 4

For Enteral Nutrition:

• At least 15 μg per 100 kcal in enteral formulas 4

Preparation and Dilution Guidelines

When Dilution is Required

• May be diluted with 0.9% Sodium Chloride, 5% Dextrose, or 5% Dextrose and Sodium Chloride 1
• All diluents must be preservative-free (benzyl alcohol is toxic to newborns) 1
• Administer immediately after mixing; discard unused portions 1
• Protect from light at all times during preparation and administration 1

Visual Inspection

• Always inspect for particulate matter and discoloration before administration 1

Special Population Considerations

High-Risk Groups Requiring Supplementation

• Exclusively breastfed infants (breast milk contains low vitamin K levels) 2
• Infants whose mothers took anticonvulsants, anticoagulants, or antituberculosis drugs 2
• Patients with fat malabsorption (cystic fibrosis, celiac disease, short bowel syndrome, cholestatic liver disease) 4
• Patients on long-term antibiotic therapy 4
• Patients with CF-related liver disease (deficiency appears universal in this population) 4

Patients on Anticoagulant Therapy

• For patients on vitamin K antagonists (warfarin), hold enteral nutrition for 1 hour before and after anticoagulant administration to prevent interactions 2
• Monitor coagulation parameters closely when administering vitamin K 2
• Doses >150 μg may cause vitamin K antagonist resistance in patients on chronic anticoagulation 4

Form Selection: Vitamin K1 vs Other Forms

• Vitamin K1 (phylloquinone/phytomenadione) is the recommended and safest form for supplementation 4, 2
• Vitamin K1 is preferred over menadione salts due to superior safety profile 4
• Vitamin K3 (menadione) should never be used as it is highly toxic and can cause jaundice, hemolytic anemia, and kernicterus in infants 4
• Vitamin K1 has at least two-fold higher efficacy than menaquinone-4 (MK-4) for normalizing coagulation 5

Monitoring and Follow-Up

Timing of Effect

• Oral administration: full effect in approximately 24 hours 2
• IV administration: maximum effect in 6-12 hours 2
• Therapeutic response for hemorrhagic disease: 2-4 hours 1

Laboratory Monitoring

• Prothrombin time (PT) is insensitive and only becomes elevated in severe deficiency 4
• PIVKA-II (protein induced by vitamin K absence) is a more sensitive marker of subclinical deficiency 4, 2
• Plasma phylloquinone <0.15 mg/L indicates depletion/deficiency 4

Common Pitfalls to Avoid

• Do not use IV route routinely—reserve only for emergencies when other routes are truly unavoidable 1
• Do not exceed 1 mg/minute infusion rate when IV administration is necessary 1
• Do not use benzyl alcohol-containing diluents in newborns 1
• Do not add vitamin K to infant feeding bottles or enteral feeds—always administer separately 4
• Do not assume vitamin K will correct coagulopathy in severe liver failure—it has minimal effect when hepatic synthetic function is severely impaired 3
• Do not routinely correct elevated INR with vitamin K in liver disease without active bleeding—this is not evidence-based 3

Toxicity and Safety

• Vitamin K1 (phylloquinone) toxicity is not a concern—no known adverse effects from supplementation 4, 2
• The only significant risk is anaphylactoid reaction with IV administration, which is rare but potentially fatal 3, 2