Vitamins are a number of chemically unrelated families of organic substances that cannot be synthesized by humans but need to be ingested in the diet in small quantities to prevent disorders of metabolism. They are divided into water-soluble and fat-soluble vitamins (table 1).More than 50 years ago, Henrik Dam of Denmark discovered an "antihemorrhagic factor" that was capable of reversing dietary-induced bleeding disorders in chicks [1]. The name "K" comes from the German/Danish word koagulationsvitamin (clotting vitamin) [2].In 1930, vitamin K was first isolated by Doisy and his colleagues, as well as by Dam, from alfalfa sprouts [3]. Until the 1980s, when chromatographic techniques were used, the mainstay of vitamin K isolation was through using chick bioassay [2].This topic review will focus on vitamin K. Overviews of the other fat-soluble vitamins, minerals and water-soluble vitamins are available elsewhere. (See "Overview of vitamin A" and "Overview of vitamin D" and "Overview of vitamin E" and "Overview of dietary trace minerals" and "Overview of water-soluble vitamins" and "Vitamin supplementation in disease prevention".)
Dietary vitamin K1 (phylloquinone or phytonadione) is found in green vegetables like spinach and broccoli (table 2) [4]. Gut micro-flora synthesizes vitamin K2 (menaquinones, including menatetrenone), which provides a portion of the dietary requirement of vitamin K [4]. Vitamin K2 has approximately 60 percent of the activity of vitamin K1, by weight, but bioavailability of both forms varies substantially depending on other intraluminal nutrients [5].vitamin K derivatives phytonadione AquaMEPHYTON, Mephyton Available forms Available by prescription only Injection (aqueous colloidal solution): 2 mg/ml Injection (aqueous dispersion): 10 mg/ml Tablets: 5 mg Indications and dosages Hypoprothrombinemia secondary to vitamin K malabsorption or drug therapy, or when oral administration is desired and bileAdults: 5 to 10 mg P.O. daily, or adjusted to patient’s needs. Hypoprothrombinemia secondary to vitamin K malabsorption, drug therapy, or excess vitamin A. Adults: 2 to 25 mg P.O. or parenterally, repeated and increased up to 50 mg, if needed.
Children: 5 to 10 mg P.O. or parenterally. Infants: 2 mg P.O. or parenterally. Hypoprothrombinemia secondary to effect of oral anticoagulants. Adults: 2.5 to 10 mg P.O., S.C., or I.M., based on PT and INR, repeated, if needed, 12 to 48 hours after oral dose or 6 to 8 hoursIn emergency, give 10 to 50 mg slow I.V., rate not to exceed 1 mg/minute, repeated q 4 hours, p.r.n. Prevention of hemorrhagic disease in neonates. Neonates: 0.5 to 1 mg S.C. or I.M. immediately (within 1 hour) after birth, repeated in 2 to 3 weeks, if needed, especially if mother received oral anticoagulants or long-term anticonvulsant therapy during pregnancy. Prevention of hypoprothrombinemia related to vitamin K deficiency in long-term parenteral nutrition. Adults: 5 to 10 mg I.M. weekly. Children: 2 to 5 mg I.M. weekly. RDA for vitamin K. Infants up to age 6 months: 5 mcg. Children ages 6 months to 1 year: 10 mcg. Children ages 1 to 3: 15 mcg. Children ages 4 to 6: 20 mcg. Children ages 7 to 10: 30 mcg.
Boys ages 11 to 14: 45 mcg. Boys ages 15 to 18: 65 mcg. Men ages 19 to 24: 70 mcg. Men older than age 24: 80 mcg. Girls ages 11 to 14: 45 mcg. Girls ages 15 to 18: 55 mcg. Women ages 19 to 24: 60 mcg. Women older than age 24: 65 mcg. Pregnant or breast-feeding women: 65 mcg. Pharmacodynamics Coagulation-modifying action: Vitamin K is a lipid-soluble vitamin that promotes hepatic formation of active prothrombin and several other coagulation factors (specifically factors II, VII, IX, and X). Phytonadione (vitamin K1) is a synthetic form of vitamin K and is also lipid-soluble. Vitamin K doesn’t counteract the action of heparin. PharmacokineticsAbsorption: Phytonadione needs the presence of bile salts for GI tract absorption. Once absorbed, vitamin K enters blood directly. of action after I.V. injection more rapid, but of shorter duration, than after S.C. or I.M. injection. Distribution: Concentrated in liver for a short time. With parenteral phytonadione, hemorrhage usually controlled within 3 to 6 hours,
and normal prothrombin levels achieved in 12 to 14 hours. Metabolism: Metabolized rapidly by liver; little tissue accumulation occurs. high levels in feces; however, intestinal bacteria can synthesize vitamin K. Contraindications and precautions Contraindicated in patients hypersensitive to drug.Broad-spectrum antibiotics (especially cefoperazone, cefotetan): May interfere with actions of vitamin K, producing hypoprothrombinemia. adjust dosage as needed.Mineral oil: Inhibits absorption of oral vitamin K. Give drugs at well-spaced intervals; Oral anticoagulants: Antagonizes effects of oral anticoagulants. Orlistat: Decreases GI absorption of fat-soluble vitamins such as vitamin K. Separate doses by at least 2 hours. Adverse reactions CNS: headache, dizziness cramplike pain, convulsive movements. CV: transient hypotension after I.V. administration, rapid and weak pulse, arrhythmias, flushing. Hematologic: fatal kernicterus, severe hemolytic anemia in neonates. pain, swelling, hematoma at injection site.
Other: anaphylaxis and anaphylactoid reactions (usually after too-rapid I.V. administration). Effects on lab test results • May increase bilirubin levels. • May decrease hemoglobin, hematocrit, PT, and INR. Overdose and treatment Excessive doses of vitamin K may cause hepatic dysfunction in adults; in neonates and premature infants, large doses may cause hemolytic anemia, kernicterus, and death. Treatment of overdose is supportive. Special considerations • If severity of condition warrants I.V. infusion, mix with preservative-free normal saline solution, D5W, or dextrose 5% in normal saline solution. • When I.V. administration is unavoidable, inject drug very slowly, not exceeding 1 mg/minute. ALERT During I.V. administration, watch for flushing, weakness, tachycardia, and hypotension; • Stop drug if allergic or severe CNS reactions appear. • Excessive use of vitamin K may temporarily defeat oral anticoagulant therapy; higher doses of oral anticoagulant or interim
use of heparin may be needed. • Monitor patient response, and watch for adverse effects; failure to respond to vitamin K may indicate coagulation defects or irreversible hepatic damage. • Phytonadione for hemorrhagic disease in infants causes fewer adverse reactions than do other vitamin K analogues; is the vitamin K analogue of choice to treat oral anticoagulant overdose. • Patients receiving phytonadione who have bile deficiency need concurrent use of bile salts to ensure adequate absorption. • Monitor PT and INR to determine effectiveness. • Phytonadione can falsely elevate urine steroid levels. Breast-feeding patients • It isn’t known if vitamin K appears in breast milk. Use cautiously in breast-feeding women. Pediatric patients • Don’t exceed recommended dosage. Hemolysis, jaundice, and hyperbilirubinemia in newborns, particularly premature infants, may be related to vitamin K administration. Patient education • For patient receiving oral form, explain rationale for drug therapy and stress importance of complying with medical regimen