warnings and cautions
5 WARNINGS AND PRECAUTIONS Do not inject intravenously, into buttock, or into digits, hands, or feet. (5.1) Hold the child’s leg firmly in place and limit movement prior to and during injection when administering to young children or infants to minimize the risk of injection-related injury. (5.1) Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection. Advise patients to seek medical care if they develop signs or symptoms of infection. (5.2) Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. (5.3) May aggravate certain coexisting conditions. (5.3) The presence of a sulfite in this product should not deter use. (5.4) 5.1 Injection-Related Complications Epinephrine Injection should only be injected into the anterolateral aspect of the thigh [see Dosage and Administration (2.2) ] . Do not inject intravenously Large doses or accidental intravenous injection of epinephrine may result in cerebral hemorrhage due to a sharp rise in blood pressure. Rapidly acting vasodilators can counteract the marked pressor effects of epinephrine for this inadvertent administration. Do not inject into buttock Injection into the buttock may not provide effective treatment of anaphylaxis. If Epinephrine Injection is injected into the buttock, advise the patient to administer a second dose of Epinephrine Injection into the anterolateral aspect of the thigh if symptoms worsen or persist, and then go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with the development of Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower the risk. Do not inject into digits, hands or feet Since 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 may not provide effective treatment of anaphylaxis. Advise the patient to administer a second dose of Epinephrine Injection into the anterolateral aspect of the thigh if experiencing anaphylaxis, and then go immediately to the nearest emergency room and inform the healthcare provider in the emergency room of the location of the accidental injection. Treatment of such inadvertent administration should consist of vasodilation, in addition to further appropriate treatment of anaphylaxis [see Adverse Reactions (6)] . Hold leg firmly during injection To minimize the risk of injection related injury when administering Epinephrine Injection to young children or infants, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection. 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. Clostridium spores can be present on the skin and introduced into the deep tissue with subcutaneous or intramuscular injection. While cleansing with alcohol may reduce presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the risk of Clostridium infection, do not inject Epinephrine Injection into the buttock [see Warnings and Precautions (5.1) ] . 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 Risks Associated with Use of Epinephrine in Certain Coexisting Conditions Some patients may be at greater risk for developing adverse reactions after epinephrine administration. Despite these concerns, it should be recognized that the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. Therefore, instruct patients with these conditions, and/or caregivers to the circumstances under which epinephrine should be used. Administer epinephrine with caution to patients who have heart disease, including patients with cardiac arrhythmias, coronary artery or organic heart disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias [see Adverse Reactions (6) and Drug Interactions (7) ] . Epinephrine can temporarily exacerbate the underlying condition or increase symptoms in patients with the following: hyperthyroidism, Parkinson’s disease, diabetes, renal impairment. Administer epinephrine with caution in patients with these conditions, including elderly patients and pregnant women. 5.4 Allergic Reactions Associated with Sulfite Epinephrine is the preferred treatment for serious allergic reactions or other emergency situations even though Epinephrine Injection contains sodium bisulfite, 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 a sulfite in Epinephrine Injection should not deter administration of the drug for treatment of serious allergic or other emergency situations.