FDA label ed5403c8-e4f3-406d-bb2c-26d7864246e1

WARNING - HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE See full prescribing information for complete boxed 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, USP. 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 [see Warnings and Precautions (5.1)]. Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after INTRAVENOUS and INTRAMUSCULAR injection of Phytonadione Injectable Emulsion, USP. 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 reasible and the serious risk is justified. (5.1)

WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactions Fatal and severe hypersensitivity reactions, including anaphylaxis, have occurred with intravenous or intramuscular administration of Phytonadione Injectable Emulsion, USP. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose. These reactions have included shock, cardiorespiratory arrest, flushing, diaphoresis, chest pain, tachycardia, cyanosis, weakness, and dyspnea. Administer Phytonadione Injectable Emulsion, USP subcutaneously whenever feasible. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified [see Dosage and Administration (2.1)] . 5.2 Risk of Serious Adverse Reaction in Infants due to Benzyl Alcohol Preservative Use benzyl alcohol-free formulations in neonates and infants, if available. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including Phytonadione. The "gasping syndrome" is characterized by central system depression, metabolic acidosis, and gasping respirations. When prescribing Phytonadione in infants, consider the combined daily metabolic load of benzyl alcohol from all sources including Phytonadione and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Use in Specific Populations (8.1, 8.2 and 8.4)] . 5.3 Cutaneous Reactions Parenteral administration of vitamin K replacements (including Phytonadione Injectable Emulsion, USP) may cause cutaneous reactions. Reactions have included eczematous reactions, scleroderma-like patches, urticaria, and delayed-type hypersensitivity reactions. Time of onset ranged from 1 day to a year after parenteral administration. Discontinue Phytonadione Injectable Emulsion, USP for skin reactions and institute medical management. Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative: Use benzyl alcohol-free formulations in neonates and infants, if available. (5.1) Cutaneous Reactions: May occur with parenteral use. Discontinue drug and manage medically. (5.3)

ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1)] Cutaneous Reactions [see Warnings and Precautions (5.3)] 6.3 Clinical Trials and Post-Marketing Experience The following adverse reactions associated with the use of Phytonadione Injectable Emulsion, USP were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size. It is not always possible to reliably estimate their frequency or establish a casual relationship to drug exposure. Cardiac Disorders: Tachycardia, hypotension. General disorders and administration site conditions: Generalized flushing; pain, swelling, and tenderness at injection site. Hepatobiliary Disorders: Hyperbilirubinemia Immune System Disorders: Fatal hypersensitivity reactions, anaphylactic reactions. Neurologic: Dysgeusia, dizziness. Pulmonary: Dyspnea. Skin and Subcutaneous Tissue Disorders: Erythema, pruritic plaques, scleroderma-like lesions, erythema perstans. Vascular: Cyanosis. Most common adverse reactions are cyanosis, diaphoresis, dizziness, dysgeusia, dyspnea, flushing, hypotension and tachycardia. (6) To report SUSPECTED ADVERSE REACTIONS, contact Amphastar Pharmaceuticals, Inc. at 1-800-423-4136, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.