SYNKAYVITE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYNKAYVITE (SYNKAYVITE).
Menadiol sodium diphosphate is a water-soluble form of vitamin K (menadione) that serves as a cofactor for the gamma-carboxylation of glutamic acid residues in clotting factors II, VII, IX, X, and proteins C and S in the liver, enabling their calcium-dependent binding to phospholipid membranes and activation of the coagulation cascade.
| Metabolism | Metabolized in the liver via conjugation with glucuronic acid and sulfate; undergoes enterohepatic circulation. |
| Excretion | Primarily fecal via bile (approximately 60-70% as metabolites, with little unchanged drug); renal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is approximately 2.5 hours (range 2-4 hours) in healthy adults; prolonged in patients with hepatic dysfunction. |
| Protein binding | Highly protein bound (99%) primarily to albumin; minimal binding to lipoproteins. |
| Volume of Distribution | Volume of distribution is approximately 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and minimal tissue sequestration. |
| Bioavailability | Oral bioavailability is variable (approximately 50-80%) due to dependence on bile salts for absorption; intramuscular bioavailability is nearly 100%. |
| Onset of Action | Intravenous: onset within 1-2 hours for reversal of coagulopathy; Intramuscular: 6-12 hours for vitamin K deficiency correction; Oral: 12-24 hours. |
| Duration of Action | Duration of effect for reversal of anticoagulation is 12-24 hours; restoration of normal prothrombin time may last 12-48 hours depending on dose and vitamin K stores. |
5 to 15 mg subcutaneously or intramuscularly once daily for 3 to 5 days; for anticoagulant reversal, 1 to 10 mg intravenously at 10 mg/min rate.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for any degree of renal impairment. |
| Liver impairment | No adjustment required for Child-Pugh A or B; use with caution in Child-Pugh C due to reduced vitamin K-dependent clotting factor synthesis. |
| Pediatric use | Neonates: 1 mg intramuscularly once; older children: 5 to 10 mg subcutaneously or intramuscularly once daily for 3 to 5 days. |
| Geriatric use | No specific dose adjustment; use same adult dosing, monitor for hypersensitivity reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYNKAYVITE (SYNKAYVITE).
| Breastfeeding | Phytonadione is excreted in human milk in low amounts. The M/P ratio is not established. Considered compatible with breastfeeding at maternal doses used for anticoagulant reversal or deficiency; minimal risk to nursing infant. No known adverse effects from infant exposure via milk. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Phytonadione (vitamin K1) crosses the placenta. Use only if clearly needed. In first trimester, theoretical risk of adverse effects but no confirmed human teratogenicity. In second and third trimesters, no known fetal harm from maternal administration at recommended doses. High doses (e.g., 10-20 mg) may cause neonatal hemolysis or kernicterus, especially in premature infants. |
■ FDA Black Box Warning
None for Synkayvite; however, parenteral formulations of vitamin K (phytonadione) have a black box warning regarding severe hypersensitivity reactions including anaphylaxis. Synkayvite is not parenterally administered.
| Serious Effects |
["Hypersensitivity to menadiol sodium diphosphate or any component of the formulation","Phenylketonuria (due to phenylalanine-containing formulations, if applicable)","In neonates with hyperbilirubinemia or immature liver function due to risk of kernicterus","Use in the treatment of hemorrhagic disease of the newborn if alternative vitamin K1 (phytonadione) is available (preferred agent)"]
| Precautions | ["May cause hemolytic anemia, hyperbilirubinemia, and kernicterus in neonates, especially premature infants, due to deficiency of glucose-6-phosphate dehydrogenase (G6PD) and immature hepatic conjugation; use with caution and monitor bilirubin levels.","Hemolysis may occur in patients with G6PD deficiency.","Allergic reactions including urticaria, erythema, and pruritus; discontinue if signs of sensitivity occur.","Large doses may produce kernicterus in neonates.","Should not be used in patients with severe hepatic disease as it may exacerbate hypoprothrombinemia."] |
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| Fetal Monitoring | Monitor maternal prothrombin time (PT) or International Normalized Ratio (INR) when used for anticoagulant reversal. In pregnancy, monitor for signs of hemorrhage or thrombosis. Fetal monitoring via ultrasound for growth and well-being if maternal condition warrants. No specific fetal monitoring required for phytonadione alone. |
| Fertility Effects | No known effects on human fertility. Animal studies have not shown impaired fertility at clinically relevant doses. |