Phytonadione is used in the prevention and treatment of hypoprothrombinemia caused by vitamin K deficiency. Phytonadione is more effective and is preferred to other vitamin K preparations in the presence of impending or actual hemorrhage. However, because phytonadione may require 3 hours or longer to stop active bleeding, administration of fresh whole blood or plasma may be necessary when bleeding is severe.
Phytonadione is the drug of choice for the treatment of moderate or severe hemorrhage caused by overdosage of coumarin or indandione derivatives, but it will not antagonize the anticoagulant action of heparin. Withdrawal of the oral anticoagulant usually corrects excessively prolonged prothrombin time or minor hemorrhage. If excessive phytonadione dosage is used, near-normal prothrombin times produced may restore the conditions that originally required administration of anticoagulant drugs, and large doses of coumarin or indandione anticoagulants may be required to reinstitute anticoagulant therapy. If anticoagulation is needed following overdosage of phytonadione, heparin may be used.
Hemorrhagic Disease of the Newborn
Phytonadione is used in the prevention and treatment of hemorrhagic disease of the newborn and is also effective in the prevention of neonatal hemorrhage resulting from anticonvulsant therapy during pregnancy. The American Academy of Pediatrics (AAP) recommends that phytonadione be routinely administered IM to infants at birth to prevent hemorrhagic disease of the newborn. Some clinicians recommend that phytonadione be administered during the last month of pregnancy (from the 36th week of gestation until delivery) to women receiving anticonvulsant therapy; however, the efficacy of such therapy has not been clearly established. Neonates whose mothers received phytonadione during pregnancy should also receive phytonadione at birth.
Hypoprothrombinemia from Other Causes
Phytonadione is used in the treatment of hypoprothrombinemia secondary to factors limiting absorption or synthesis of Vitamin K. Although dietary sources of vitamin K are usually adequate (except during the first 5-8 days of the neonatal period), deficiency can occur in infants who are breast-fed and in patients receiving prolonged hyperalimentation, as well as in the presence of malabsorption syndromes such as sprue, celiac disease, ulcerative colitis, regional enteritis, cystic fibrosis, prolonged diarrhea, obstructive jaundice, internal biliary fistula, dysentery, and after extensive bowel resection. Diagnosis of vitamin K deficiency may be based on tests for vitamin K-dependent clotting factors (e.g., prothrombin time, which is sensitive to the levels of factors II, VII, and X) or on a therapeutic trial of phytonadione.
Phytonadione may also be valuable in restoring normal clotting time in hypoprothrombinemia induced by salicylates, sulfonamides, quinine, quinidine, or broad-spectrum antibiotic therapy, when it is definitely caused by interference with vitamin K activity. If possible, discontinuance or reduction of the dosage of drugs interfering with the coagulation mechanism should be used as an alternative to phytonadione therapy.
Phytonadione is ineffective in the treatment of hereditary hypoprothrombinemia. The drug is also ineffective in reversing hypoprothrombinemia caused by severe liver disease, and high doses may prolong the prothrombin time and aggravate the disease. Failure to respond to a test dose of phytonadione indicates a disorder that is not vitamin K-dependent, and repeated large doses of the drug are contraindicated.
The National Academy of Sciences (NAS) has issued a comprehensive set of Recommended Dietary Allowances (RDAs) as reference values for dietary nutrient intakes since 1941. In 1997, the NAS Food and Nutrition Board (part of the Institute of Medicine [IOM]) announced that they would begin issuing revised nutrient recommendations that would replace RDAs with Dietary Reference Intakes (DRIs). DRIs are reference values that can be used for planning and assessing diets for healthy populations and for many other purposes and that encompass the Estimated Average Requirement (EAR), the Recommended Dietary Allowance (RDA), the Adequate Intake (AI), and the Tolerable Upper Intake Level (UL).
Because of the lack of adequate data, the NAS was unable to establish accurate EARs and RDAs for vitamin K. The NAS has established an AI for vitamin K for adults, adolescents, and children 1 year of age or older based on reported vitamin K dietary intake in apparently healthy population groups (Third National Health and Nutrition Examination Survey [NHANES III]). Dietary intakes reportedly are slightly lower in women than men. An AI has been established for infants through 6 months of age based on the observed mean vitamin K intake of infants fed principally human milk. An AI for infants 7-12 months of age has been set based on the AI for younger infants. (For a definition of Estimated Average Intake, Recommended Dietary Allowance, Adequate Intake, and other reference values for dietary nutrient intakes, .)
The principal goal of maintaining an adequate intake of vitamin K in the US and Canada is to prevent Vitamin K deficiency, and thus prevent vitamin K-responsive hypothrombinemia. Adequate intake of vitamin K usually can be accomplished through consumption of foodstuffs. Spinach, collards, broccoli, iceberg lettuce, and plant oils are the major contributors of vitamin K in the diet of US adults and children.
For specific information on currently recommended AIs of vitamin K for various life-stage and gender groups,
see Dosage: Dietary and Replacement Requirements, under Dosage and Administration.