t a clotting agent, but overzealous therapy with vitamin k 1 may restore conditions which originally permitted thromboembolic phenomena. dosage should be kept as low as possible, and prothrombin time should be checked regularly as clinical conditions indicate. repeated large doses of vitamin k are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. failure to respond to vitamin k may indicate that the condition being treated is inherently unresponsive to vitamin k. benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in premature infants. warning: this product contains aluminum that may be toxic. aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. premature neonates are particularly at risk because their kidneys are immature, and they required large amounts of calcium and phosphate solutions, which contain aluminum. research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. tissue loading may occur at even lower rates of administration.

should be discarded, as well as unused contents of the ampul. prophylaxis of hemorrhagic disease of the newborn the american academy of pediatrics recommends that vitamin k 1 be given to the newborn. a single intramuscular dose of vitamin k 1 injection 0.5 to 1 mg within one hour of birth is recommended. treatment of hemorrhagic disease of the newborn empiric administration of vitamin k 1 should not replace proper laboratory evaluation of the coagulation mechanism. a prompt response (shortening of the prothrombin time in 2 to 4 hours) following administration of vitamin k 1 is usually diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder. vitamin k 1 injection 1 mg should be given either subcutaneously or intramuscularly. higher doses may be necessary if the mother has been receiving oral anticoagulants. whole blood or component therapy may be indicated if bleeding is excessive. this therapy, however, does not correct the underlying disorder and vitamin k 1 injection should be given concurrently. anticoagulant-induced prothrombin deficiency in adults to correct excessively prolonged prothrombin time caused by oral anticoagulant therapy—2.5 to 10 mg or up to 25 mg initially is recommended. in rare instances 50 mg may be required. frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition (see warnings ). if in 6 to 8 hours after parenteral administration the prothrombin time has not been shortened satisfactorily, the dose should be repeated. vitamin k 1 injection (phytonadione injectable emulsion, usp) summary of dosage guidelines (see circular text for details) newborns dosage hemorrhagic disease of the newborn prophylaxis 0.5 to 1 mg im within 1 hour of birth treatment 1 mg sc or im (higher doses may be necessary if the mother has been receiving oral anticoagulants) adults initial dosage anticoagulant-induced prothrombin deficiency (caused by coumarin or indanedione derivatives) 2.5 mg to 10 mg or up to 25 mg (rarely 50 mg) hypoprothrombinemia due to other causes (antibiotics; salicylates or other drugs; factors limiting absorption or synthesis) 2.5 mg to 25 mg or more (rarely up to 50 mg) in the event of shock or excessive blood loss, the use of whole blood or component therapy is indicated. hypoprothrombinemia due to other causes in adults a dosage of 2.5 to 25 mg or more (rarely up to 50 mg) is recommended, the amount and route of administration depending upon the severity of the condition and response obtained. if possible, discontinuation or reduction of the dosage of drugs interfering with coagulation mechanisms (such as salicylates; antibiotics) is suggested as an alternative to administering concurrent vitamin k 1 injection. the severity of the coagulation disorder should determine whether the immediate administration of vitamin k 1 injection is required in addition to discontinuation or reduction of interfering drugs.

bsorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. very little vitamin k accumulates in tissues. little is known about the metabolic fate of vitamin k. almost no free unmetabolized vitamin k appears in bile or urine. in normal animals and humans, phytonadione is virtually devoid of pharmacodynamic activity. however, in animals and humans deficient in vitamin k, the pharmacological action of vitamin k is related to its normal physiological function, that is, to promote the hepatic biosynthesis of vitamin k dependent clotting factors. the action of the aqueous dispersion, when administered intravenously, is generally detectable within an hour or two and hemorrhage is usually controlled within 3 to 6 hours. a normal prothrombin level may often be obtained in 12 to 14 hours. in the prophylaxis and treatment of hemorrhagic disease of the newborn, phytonadione has demonstrated a greater margin of safety than that of the water-soluble vitamin k analogues.