warnings and cautions
5 WARNINGS AND PRECAUTIONS • Do not inject into buttocks, digits, hands, or feet. ( 5.1 ) • Avoid extravasation into tissues, which can cause local necrosis. ( 5.3 ) • Monitor patient for acute severe hypertension. ( 5.4 ) • Potential for pulmonary edema, which may be fatal. ( 5.5 ) • May constrict renal blood vessels and decrease urine formation. ( 5.6 ) • May induce potentially serious cardiac arrhythmias or aggravate angina • pectoris, particularly in patients with underlying heart disease. ( 5.7 ) • Presence of sulfite in this product should not deter use. ( 5.8 ) 5.1 Injection-Related Complications for Anaphylaxis Injection into the anterolateral aspect of the thigh (vastus lateralis muscle) is the most appropriate location for administration because of its location, size, and available blood flow. Injection into (or near) smaller muscles, such as in the deltoid, is not recommended. Do not administer repeated injections of epinephrine at the same site, as the resulting vasoconstriction may cause tissue necrosis. Do Not Inject Intravenously Large doses or accidental intravenous injection of undiluted epinephrine may result in cerebral hemorrhage due to sharp rise in blood pressure. Rapidly acting vasodilators can counteract the marked pressor effects of epinephrine if there is such inadvertent administration. Do not inject into buttock. Injection into the buttock may not provide effective treatment of anaphylaxis and has been associated with the development of Clostridial infections (gas gangrene). Do not inject into digits, hands, or feet. Epinephrine is a strong vasoconstrictor. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area and tissue necrosis. 5.2 Serious Infections at the Injection Site Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site. 5.3 Extravasation and Tissue Necrosis with Intravenous Infusion Avoid extravasation of epinephrine into the tissues, to prevent local necrosis. When Epinephrine Injection is administered intravenously, the infusion site should be checked 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 superficial slough. Hence, if blanching occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside. There is a 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. 5.4 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. 5.5 Pulmonary Edema Epinephrine increases cardiac output and causes peripheral vasoconstriction, which may result in pulmonary edema. 5.6 Renal Impairment Epinephrine constricts renal blood vessels, which may result in oliguria or renal impairment. 5.7 Cardiac Arrhythmias and Ischemia Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients suffering from coronary artery disease, or cardiomyopathy. 5.8 Allergic Reactions Associated with Sulfite Epinephrine is the preferred treatment for serious allergic or other emergency situations even though this product contains sodium metabisulfite, a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life threatening situation may not be satisfactory. The presence of sulfite(s) in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations.