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 bile secretion is inadequate. Adults: 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 hours after parenteral dose. In 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.

Pharmacokinetics
Absorption: Phytonadione needs the presence of bile salts for GI tract absorption. Once absorbed, vitamin K enters blood directly. Onset 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.
Excretion: Limited data; high levels in feces; however, intestinal bacteria can synthesize vitamin K.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug.

Interactions
Drug-drug. Broad-spectrum antibiotics (especially cefoperazone, cefotetan): May interfere with actions of vitamin K, producing hypoprothrombinemia. Avoid use together; adjust dosage as needed.
Mineral oil: Inhibits absorption of oral vitamin K. Give drugs at well-spaced intervals; monitor result.
Oral anticoagulants: Antagonizes effects of oral anticoagulants. Avoid use together.
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.
GI: nausea, vomiting.
Hematologic: fatal kernicterus, severe hemolytic anemia in neonates.
Hepatic: hyperbilirubinemia.
Respiratory: bronchospasm, dyspnea.
Skin: diaphoresis; erythema; urticaria; pruritus; allergic rash; 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; shock may follow. Deaths have occurred.
• 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; phytonadione 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 and keeping follow-up appointments.
• Tell patient to take a missed dose as soon as possible (but not if it’s almost time for next dose) and to report missed doses.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use