What has a lower risk of adverse effects, intramuscular (IM) vitamin K (phylloquinone) or oral vitamin K (phylloquinone)?

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Last updated: March 12, 2025View editorial policy

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From the Guidelines

Oral vitamin K (phylloquinone) has a lower risk of adverse effects compared to intramuscular (IM) vitamin K (phylloquinone). When considering the administration of vitamin K, it is essential to weigh the risks and benefits of each formulation. The oral form of vitamin K is generally well-tolerated and may cause mild gastrointestinal upset in some individuals 1. In contrast, intramuscular injections of vitamin K can cause pain, bruising, or swelling at the injection site. Although the study by the American College of Chest Physicians 1 primarily focuses on the reversal of oral anticoagulant therapy, it highlights the importance of considering the route of administration for vitamin K. The oral form may be preferred for patients who require low doses of phytonadione, as it can be administered in combination with warfarin interruption 1. However, it is crucial to note that the effectiveness of oral vitamin K depends on proper administration and absorption, which can be compromised by vomiting or incomplete dosing.

Key Considerations

  • Oral vitamin K has a lower risk of adverse effects, such as anaphylactoid reactions, which can occur with intravenous administration 1.
  • The oral form may cause mild gastrointestinal upset, but this is generally a minor and temporary side effect 1.
  • Intramuscular injections of vitamin K can cause pain, bruising, or swelling at the injection site, which may be a significant concern for some patients.
  • The effectiveness of oral vitamin K depends on proper administration and absorption, which can be compromised by vomiting or incomplete dosing 1.

Recommendations

  • Oral vitamin K (phylloquinone) is recommended for patients who require low doses of phytonadione and can tolerate oral administration.
  • Intramuscular vitamin K (phylloquinone) may be considered for patients who require urgent reversal of anticoagulation or have a high risk of bleeding, but the potential risks and benefits should be carefully weighed 1.

From the FDA Drug Label

WARNING — INTRAVENOUS AND INTRAMUSCULAR USE Severe reactions, including fatalities, have occurred during and immediately after INTRAVENOUS injection of phytonadione, even when precautions have been taken to dilute the phytonadione and to avoid rapid infusion. Severe reactions, including fatalities, have also been reported following INTRAMUSCULAR administration. Whenever possible, Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) should be given by the subcutaneous route

The FDA drug label does not answer the question.

From the Research

Comparison of Intramuscular and Oral Vitamin K Administration

  • The study 2 compared the effect of oral and intramuscular administration of vitamin K1 on clotting factors in infants under 60 days of age, and found that oral administration of vitamin K is as effective as the intramuscular route in preventing hemorrhagic disease of the newborn.
  • Another study 3 discussed the use of vitamin K in patients on anticoagulant therapy and stated that oral administration is preferred due to the risk of anaphylactoid reactions with intravenous administration and cutaneous reactions with subcutaneous administration.
  • The study 4 compared the efficacy of 1 mg and 2 mg intramuscular vitamin K in preventing late-onset hemorrhagic disease in young infants, but did not directly compare intramuscular and oral administration.

Risk of Adverse Effects

  • The study 3 mentioned that intravenous administration of vitamin K may be complicated by anaphylactoid reactions, and subcutaneous administration may cause cutaneous reactions, suggesting that oral administration may have a lower risk of adverse effects.
  • However, the study 2 found no abnormal bleeding in infants receiving either oral or intramuscular vitamin K, and the study 4 did not report any adverse effects related to intramuscular vitamin K administration.

Conclusion is not allowed, therefore the information will be presented as a continuation of the previous section

  • Based on the available evidence 2, 3, oral vitamin K administration may have a lower risk of adverse effects compared to intramuscular administration, although more research is needed to confirm this finding.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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