FDA label d576d2a7-cb16-3c15-e053-2a95a90ac40b

5 WARNINGS AND PRECAUTIONS Do not inject into buttocks, digits, hands, or feet ( 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 ) May aggravate angina pectoris or produce ventricular arrhythmias, particularly in patients with underlying heart disease, administer with caution when used intramuscularly or subcutaneously ( 5.3 ) Patients with hyperthyroidism, Parkinson's disease, diabetes, and pheochromocytoma are at greater risk of having adverse reactions when used intramuscularly or subcutaneously ( 5.3 ) Presence of sulfite in this product should not deter use for anaphylaxis ( 5.4 ) The Epinephrine does not have markings for doses less than 0.15mL or 0.15mg 5.1 Incorrect Locations of Injection 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 due to possible differences in absorption associated with this use. Do not administer repeated injections of epinephrine at the same site, as the resulting vasoconstriction may cause tissue necrosis. 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). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower this risk. 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 has been associated with 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. 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 Adrenalin ® 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 Disease Interactions Some patients may be at greater risk for developing adverse reactions after systemic epinephrine administration. Despite these concerns, the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. Patients with Heart Disease Epinephrine should be administered with caution in patients who have heart disease, including patients with cardiac arrhythmias, coronary artery or organic heart disease, cerebrovascular 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 Drug Interactions (7) and Adverse Reactions (6) ]. Other Patients and Diseases Epinephrine should be administered with caution to patients with hyperthyroidism, Parkinson's disease, diabetes mellitus, pheochromocytoma, elderly individuals, and pregnant women. Patients with Parkinson's disease may experience psychomotor agitation or notice a temporary worsening of symptoms. Diabetic patients may experience transient increases in blood sugar. 5.4 Allergic Reactions Associated with Sulfite Adrenalin ® contains sodium bisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals. However, the presence of bisulfite in this product should not preclude its use for the treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory.

6 ADVERSE REACTIONS Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [ see Warnings and Precautions (5.3) ]. Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below by body system: Cardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy. Angina may occur in patients with coronary artery disease [ see Warnings and Precautions (5.3) ]. Arrhythmias, including fatal ventricular fibrillation, have occurred, particularly in patients with underlying organic heart disease or patients receiving drugs that sensitize the heart to arrhythmias [ see Warnings and Precautions (5.3) ]. Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [ see Warnings and Precautions (5.3) ]. Respiratory: respiratory difficulties. Neurological: dizziness , disorientation , excitability , headache , impaired memory , lightheadedness , nervousness , panic, psychomotor agitation, sleepiness , tingling , tremor, and weakness. Psychiatric: anxiety, apprehensiveness, restlessness. Gastrointestinal: nausea, vomiting. Other: Patients with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms [ see Warnings and Precautions (5.3) ]. Diabetic patients may experience transient increases in blood sugar [ see Warnings and Precautions (5.3) ]. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [ see Warnings and Precautions (5.1) ]. Adverse events experienced as a result of an injection into these areas include increased heart rate, local reactions including injection site pallor, coldness, hypoesthesia, and tissue loss, or injury at the injection site resulting in bruising, bleeding, discoloration, erythema, and skeletal injury. Injection into the buttock has resulted in cases of gas gangrene [ see Warnings and Precautions (5.1) ]. Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [see Warnings and Precautions (5.2) ] . Skin: sweating. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and 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 Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.