EPINEPHRINE

5 WARNINGS AND PRECAUTIONS Monitor patient for acute severe hypertension. ( 5.1 ) Potential for pulmonary edema, which may be fatal. ( 5.2 ) May induce potentially serious cardiac arrhythmias and myocardial ischemia, particularly in patients with underlying heart disease. ( 5.3 ) Avoid extravasation into tissues, which can cause local necrosis. ( 5.4 ) Potential for oliguria or renal impairment. ( 5.5 ) Presence of sulfite in this product should not deter use for hypotension associated with septic shock ( 5.6 ) 5.1 Hypertension Because individual response to epinephrine may vary significantly, monitor blood pressure frequently and titrate to avoid excessive increases in blood pressure. Patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may experience severe, prolonged hypertension when given epinephrine. 5.2 Pulmonary Edema Epinephrine increases cardiac output and causes peripheral vasoconstriction, which may result in pulmonary edema. 5.3 Cardiac Arrhythmias and Ischemia Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients with coronary artery disease, or cardiomyopathy [see Adverse Reactions and Drug Interactions (7.3) ] . 5.4 Extravasation and Tissue Necrosis with Intravenous Infusion Avoid extravasation of epinephrine into the tissues, to prevent local necrosis. When Epinephrine Injection is administered intravenously, check the infusion site frequently for free flow. Blanching along the course of the infused vein, sometimes without obvious extravasation, may be attributed to vasa vasorum constriction with increased permeability of the vein wall, permitting some leakage. This also may progress on rare occasions to a superficial slough. Hence, if blanching occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside. There is potential for gangrene in a lower extremity when infusions of catecholamine are given in an ankle vein. Antidote for Extravasation Ischemia: To prevent sloughing and necrosis in areas in which extravasation has taken place, infiltrate the area with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic blocking agent. Use a syringe with a fine hypodermic needle, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.5 Renal Impairment Epinephrine constricts renal blood vessels, which may result in oliguria or renal impairment. 5.6 Allergic Reactions associated with Sulfite Epinephrine Injection contains sodium metabisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes, particularly in patients with a history of allergies. The presence of sodium metabisulfite in this product should not preclude its use for the treatment of hypotension associated with septic shock even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory. In susceptible patients, consider using a formulation of epinephrine or another vasoconstrictor that does not contain sodium metabisulfite.

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in labeling: Hypertension [see Warnings and Precautions (5.1) ] Pulmonary Edema [see Warnings and Precautions (5.2) ] Cardiac Arrhythmias and Ischemia [see Warnings and Precautions (5.3) ] Extravasation and Tissue Necrosis with Intravenous Infusion [see Warnings and Precautions (5.4) ] Renal Impairment [see Warnings and Precautions (5.5) ] Allergic Reactions associated with Sulfite [see Warnings and Precautions (5.6) ] The following adverse reactions have been associated with use of epinephrine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Cardiovascular disorders : tachycardia, supraventricular tachycardia, ventricular arrhythmias (including fatal ventricular fibrillation), myocardial ischemia, myocardial infarction, limb ischemia, pulmonary edema, hypertension Gastrointestinal disorders : nausea, vomiting General disorders and administrative site conditions : extravasation Metabolic : insulin resistance, hypokalemia, lactic acidosis Nervous system disorders : headache, paresthesia, tremor, stroke, central nervous system bleeding, weakness, dizziness, disorientation, impaired memory, panic, psychomotor agitation, somnolence Psychiatric disorders : excitability, anxiety, apprehensiveness, nervousness, restlessness Renal disorders : renal insufficiency Respiratory : rales Skin and subcutaneous tissue disorders : diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation. Most common adverse reactions to systemically administered epinephrine are headache; anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; diaphoresis; nausea/vomiting; and/or respiratory difficulties. Arrhythmias, including fatal ventricular fibrillation, rapid rises in blood pressure producing cerebral hemorrhage, and angina have occurred. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .