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INTRODUCTION

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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 xenobiotic induced vitamin K deficiency. Acquired vitamin K deficiency typically results from the therapeutic administration of warfarin, or following the 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 is 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 may be associated with anaphylactoid reactions, it should be avoided unless serious or life-threatening bleeding is present. Subcutaneous administration should only be considered when a patient is unable to tolerate oral vitamin K therapy and is not clinically compromised enough to necessitate IV vitamin K1.8

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HISTORY

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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.19,32,37

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PHARMACOLOGY

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Chemistry

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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).

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Related Vitamin K Compounds

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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. In addition, patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased risk of hemolysis with other vitamin K preparations. 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.15,34

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Vitamins K3 (menadione) and K4 (menadiol sodium diphosphate) are no longer approved by the US Food and Drug Administration, (FDA) because they can 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 that these preparations are absorbed directly from the intestine by a passive process that does not require the presence of bile salts. Theoretically, they are advantageous for patients ...

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