TY - CHAP M1 - Book, Section TI - VITAMIN K1 (PHYTONADIONE) A1 - Kearney, Thomas E. A2 - Olson, Kent R. A2 - Anderson, Ilene B. A2 - Benowitz, Neal L. A2 - Blanc, Paul D. A2 - Clark, Richard F. A2 - Kearney, Thomas E. A2 - Kim-Katz, Susan Y. A2 - Wu, Alan H. B. PY - 2018 T2 - Poisoning & Drug Overdose, 7e AB - Pharmacology. Vitamin K1 is an essential cofactor in the hepatic synthesis of coagulation factors II, VII, IX, and X. In adequate doses, vitamin K1 reverses the inhibitory effects of coumarin and indanedione derivatives on the synthesis of these factors. Note: Vitamin K3 (menadione) is not effective in reversing excessive anticoagulation caused by these agents. After parenteral vitamin K1 administration, there is a 6- to 8-hour delay before vitamin K-dependent coagulation factors begin to achieve significant levels, and peak effects are not seen until 1–2 days after the initiation of therapy. The duration of effect is 5–10 days. The response to vitamin K1 is variable, and the optimal dosage regimen is unknown; it is influenced by the potency and amount of the ingested anticoagulant, vitamin K pharmacokinetics, and the patient's hepatic biosynthetic capability.IndicationsExcessive anticoagulation caused by coumarin and indanedione derivatives, as evidenced by an elevated prothrombin time (Warfarin and Superwarfarins). Vitamin K1 is not indicated for empiric treatment of anticoagulant ingestion, as most cases do not require treatment, and its use will delay the onset of an elevated prothrombin time as a marker of a toxic ingestion.Vitamin K deficiency (eg, malnutrition, malabsorption, or hemorrhagic disease of the newborn) with coagulopathy.Hypoprothrombinemia resulting from salicylate intoxication.Contraindications. Do not use in patients with known hypersensitivity to vitamin K or preservatives.Adverse effectsBlack box warning. Anaphylactoid reactions have been reported after intravenous administration and have been associated with fatalities. Although these are rare (incidence of 3 cases per 10,000 doses), intravenous use should be restricted to true emergencies; the patient must be monitored closely in an intensive care setting, and reducing the infusion rate may reduce the risk. Severe reactions and fatalities have also been associated with intramuscular administration and resembled hypersensitivity reactions.Intramuscular administration in patients receiving anticoagulants may cause large, painful hematomas. This can be avoided by using the oral or subcutaneous route.Patients receiving anticoagulants for medical reasons (eg, deep vein thrombosis or prosthetic heart valves) may experience untoward effects from complete reversal of their anticoagulation status. Therapy in such patients should be based on the INR and presence or risk of bleeding.Use in pregnancy. FDA Category C (indeterminate). Vitamin K1 crosses the placenta readily. However, this does not preclude its acute, short-term use in a seriously symptomatic patient (Introduction).Drug or laboratory interactions. Empiric use after an acute anticoagulant overdose will delay (for up to several days) the onset of elevation of the prothrombin time, and this may give a false impression of insignificant ingestion in a case of serious "superwarfarin" overdose.Dosage and method of administrationOral.Reversal of therapeutic warfarin effect:If INR less than 5 and no significant bleeding: hold warfarin dose, no vitamin K needed.If INR 5–9 and no bleeding: hold warfarin dose and administer small titrated oral doses (1-2.5 mg) of vitamin K.If INR exceeds 9 and no bleeding present, or only minor bleeding present regardless of INR: hold warfarin dose and administer 2.5–5 mg of oral vitamin K.If serious hemorrhage is present (regardless of INR): hold warfarin dose and administer 10 mg of vitamin K ... SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessmedicine.mhmedical.com/content.aspx?aid=1174607588 ER -