Vitamin K administration – Routes comparison

Let’s start with a patient case.  A patient is admitted to the hospital with a CHF exacerbation.  They are taking warfarin for atrial fibrillation and their coagulation panel reveals an INR of 8.  What are our options for administering vitamin K and some of the nuances for each route of administration?

Scenarios similar to this are common occurrences in the internal medicine setting as heart failure is an independent risk factor for overanticoagulation.  The decision whether or not to use vitamin K should be based on several factors which will not be addressed now.

Vitamin K can be administered by the oral, intravenous, intramuscular, or subcutaneous routes.  Vitamin K is a fat-soluble vitamin of which there are two types; one we find in green vegetables (and lots of other foods) and the other is synthesized by intestinal bacteria.  The vitamin K that we give for therapeutic use is the former, phytonadione.¹

Oral:

• Phytonadione is absorbed in the proximal small intestine and requires lymph and bile for absorption.  In someone who lacks bile, hypoprothrombinemia develops slowly over several weeks.¹  When warfarin is held and oral phytonadione is given, it takes approximately 1.4 days for an INR of 6 to 10 to decline to <4.  At 24 hours, the effects of 5 mg of oral vitamin K on INR is roughly equal to 1 mg of intravenous vitamin K.²  Generally use doses of 2.5 to 5 mg.

Intravenous:

• When given at high doses (5-10 mg), intravenous works more quickly than oral (within 2 hours) and the INR should correct to close to normal in 24 hours.  The intravenous route may cause anaphylactoid reactions (3/10,000 doses) so should be diluted and administered over at least 20 minutes.  Deaths due to this reaction have still occurred when correctly following these precautions.²

Intramuscular:

• Carries same risk for anaphylactoid reactions as intravenous route.  Skin lesions and cutaneous reactions have been reported.³

Subcutaneous:

• Less effective than low dose oral phytonadione.² Meta-analysis shows correction of overanticoagulation no different from placebo or observation.⁴

Take home points:

• At 24 hours, 5mg po = 1mg IV
• Oral/low dose IV (1mg) – INR 6 to 10 decreases to <4 in 36 hours
• High dose IV (10mg) – INR decreases to normal in 24 hours
• IV & IM both can cause anaphylactoid reactions and should be reserved for serious bleeding

Note:  This discussion is in reference to vitamin K for reversal of overanticoagulation due to vitamin K antagonist use in adults in those without prosthetic heart valves.  There are other options besides vitamin K that were not addressed.  INR effects are assuming patient’s liver has synthetic function intact.

References:

1.  Weitz JI. Chapter 30. Blood Coagulation and Anticoagulant, Fibrinolytic, and Antiplatelet Drugs.  In: Brunton LL, Chabner BA, Knollman BC, eds.  Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011.

2.  Ageno W, Gallus AS, Wittkowsky A, et al.  Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9^th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e44S-e88S.

3.  Phytonadione. Micromedex. Available at: www.micromedexsolutions.com

4.  Dezee KJ, Shimeall WT, Douglas KM, et al.  Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med. 2006;166(4):391.

photo by katerha