⛔ FDA Black Box Warning
WARNING – HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after intravenous and intramuscular injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified [ see Warnings and Precautions (5.1) ] . WARNING – HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE See full prescribing information for complete boxed warning . Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after INTRAVENOUS and INTRAMUSCULAR injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid infusion and upon first and subsequent doses. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified. ( 5.1 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary If phytonadione is needed during pregnancy, consider using a preservative-free formulation. Published studies with the use of phytonadione during pregnancy have not reported a clear association with phytonadione and adverse developmental outcomes (see Data ) . There are maternal and fetal risks associated with vitamin K deficiency during pregnancy (see Clinical Considerations ) . Animal reproduction studies have not been conducted with phytonadione. The estimated background risk for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnant women with vitamin K deficiency hypoprothrombinemia may be at an increased risk for bleeding diatheses during pregnancy and hemorrhagic events at delivery. Subclinical maternal vitamin K deficiency during pregnancy has been implicated in rare cases of fetal intracranial hemorrhage. Data Human Data Phytonadione has been measured in cord blood of infants whose mothers were treated with phytonadione during pregnancy in concentrations lower than seen in maternal plasma. Administration of vitamin K 1 to pregnant women shortly before delivery increased both maternal and cord blood concentrations. Published data do not report a clear association with phytonadione and adverse maternal or fetal outcomes when used during pregnancy. However, these studies cannot definitively establish the absence of any risk because of methodologic limitations including small sample size and lack of blinding. Animal Data In pregnant rats receiving vitamin K 1 orally, fetal plasma and liver concentrations increased following administration, supporting placental transfer.