Chapter A18: Vitamin K₁

INTRODUCTION

Vitamin K₁ (phytonadione) is the commercial preparation of the natural form of vitamin K (phylloquinone) that is indicated for the reversal of an elevated prothrombin time (PT) or an international normalized ratio (INR) in patients with vitamin K deficiency. Acquired vitamin K deficiency most commonly results from the therapeutic administration of warfarin or after an overdose of warfarin or a long-acting anticoagulant rodenticide (LAARs), such as brodifacoum. The optimal dosage regimen of vitamin K₁ to treat patients who develop an elevated INR while receiving warfarin was given in the 2012 American College of Chest Physicians consensus guidelines.¹ Oral administration of vitamin K₁ is safe and effective. Because intravenous (IV) administration of vitamin K₁ is associated with anaphylactoid reactions, its use is not recommended unless serious or life-threatening hemorrhage is present. Subcutaneous (SC) administration should only be used when a patient is unable to tolerate oral vitamin K therapy and is not clinically compromised enough to necessitate IV vitamin K₁.¹⁰

HISTORY

It was noted in 1929 that chickens fed a poor diet developed spontaneous bleeding. In 1935, Dam and coworkers discovered that incorporating a fat-soluble substance, defined as a “koagulation factor,” into the diet could correct the bleeding, leading to the name vitamin K.^23,40,45

PHARMACOLOGY

Chemistry

Vitamin K is an essential fat-soluble vitamin that encompasses at least two distinct natural forms. Vitamin K₁ (phytonadione, phylloquinone) is the only form synthesized by plants and algae. Vitamin K₂ (menaquinones) is actually a series of compounds with the same 2-methyl-1, 4-naphthoquinone ring structure as phylloquinone but with a variable number (1–13) of repeating five-carbon units on the side chain. Bacteria synthesize vitamin K₂ (menaquinones). Most of the vitamin K ingested in the diet is phylloquinone (vitamin K₁).

Related Vitamin K Compounds

Vitamin K₁ (phytonadione) is the only vitamin K preparation that should be used to reverse anticoagulant-induced vitamin K deficiency or to treat infants or pregnant women. Vitamin K₁ is superior to the other previously commercially available vitamin K preparations because it is more active, requires smaller doses, and has fewer associated risks.^19,42 In addition, patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased risk of hemolysis with other vitamin K preparations.

Vitamins K₃ (menadione) and K₄ (menadiol sodium diphosphate) are no longer approved by the US Food and Drug Administration (FDA) because they produce hemolysis, hyperbilirubinemia, and kernicterus in neonates, as well as hemolysis in G6PD-deficient patients. The only advantage that menadione and menadiol sodium diphosphate have is their direct absorption from the intestine by a passive process that does not require the presence of bile salts. However, even for patients with cholestasis or ...