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1 INDICATIONS AND USAGE AUVI-Q is indicated for the emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients who weigh 7.5 kg or greater. AUVI-Q is a non-selective alpha and beta-adrenergic receptor agonist indicated for the emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients who weigh 7.5 kg or greater. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage of AUVI-Q is based on weight. ( 2.1 ) Administer AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. ( 2.2 ) Recommended Dosage Patient’s Weight Dosage 30 kg or greater AUVI-Q 0.3 mg 15 kg to less than 30 kg AUVI-Q 0.15 mg 7.5 kg to less than 15 kg AUVI-Q 0.1 mg In the absence of clinical improvement or if symptoms worsen after the initial treatment, a second dose of AUVI-Q may be administered with a second autoinjector starting 5 minutes after the first dose. ( 2.1 ) Advise patients when to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required. ( 2.1 ) It is recommended that patients are prescribed and have immediate access to two AUVI-Q devices at all times. ( 2.1 ) See full prescribing information for administration instructions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage for patients who weigh 7.5 kg or greater is based on weight and the dosage is provided in Table 1 . Administer AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh. Table 1. Recommended Dosage of AUVI-Q Based on Patient’s Weight Patient’s Weight Dosage 30 kg or greater AUVI-Q 0.3 mg 15 kg to less than 30 kg AUVI-Q 0.15 mg 7.5 kg to less than 15 kg AUVI-Q 0.1 mg Since the doses of epinephrine delivered from AUVI-Q are fixed, use other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary. In the absence of clinical improvement or if symptoms worsen after the initial treatment, a second dose of AUVI-Q may be administered with a second autoinjector starting 5 minutes after the first dose. Advise patients when to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required. It is recommended that patients are prescribed and have immediate access to two AUVI-Q devices at all times. 2.2 Administration Instructions Each AUVI-Q contains a single dose of epinephrine for single use. Visually inspect the epinephrine solution in the viewing window of AUVI-Q for particulate matter, cloudiness, and discoloration prior to administration. Instruct caregivers of young children and infants who are prescribed AUVI-Q and who may be uncooperative and kick or move during an injection to hold the child’s leg firmly in place and limit movement prior to and during an injection [see Warnings and Precautions ( 5.1 )] . Inject AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject intravenously, and do not inject into buttocks, digits, hands or feet [see Warnings and Precautions ( 5.1 )] . If a second dose is needed, administer a new AUVI-Q starting 5 minutes after the first dose. More than two sequential doses of epinephrine should be administered under direct medical supervision. Refer patients and caregivers to the Instructions for Use for detailed administration instructions.

3 DOSAGE FORMS AND STRENGTHS Injection: 0.3 mg (0.3 mg/0.3 mL) epinephrine injection, USP, clear and colorless solution, single-dose prefilled autoinjector 0.15 mg (0.15 mg/0.15 mL) epinephrine injection, USP, clear and colorless solution, single-dose prefilled autoinjector 0.1 mg (0.1 mg/0.1 mL) epinephrine injection, USP, clear and colorless solution, single-dose prefilled autoinjector Injection: 0.3 mg (0.3 mg/0.3 mL) epinephrine in a single-dose prefilled autoinjector ( 3 ) 0.15mg (0.15 mg/0.15 mL) epinephrine in a single-dose prefilled autoinjector ( 3 ) 0.1 mg (0.1 mg/0.1 mL) epinephrine in a single-dose prefilled autoinjector ( 3 )

5 WARNINGS AND PRECAUTIONS Do not inject intravenously, into buttock, 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 AUVI-Q should only be injected into the anterolateral aspect of the thigh [see Dosage and Administration ( 2.1 , 2.2 )] . Do not inject intravenously. Large doses or accidental intravenous injection of epinephrine may result in cerebral hemorrhage due to 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 AUVI-Q is injected into the buttock, advise the patient to administer a second dose of AUVI-Q into the anterolateral aspect of the thigh and if symptoms worsen or persist, then go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with 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. 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 AUVI-Q 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 AUVI-Q 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 the presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the risk of Clostridium infection, do not inject AUVI-Q into the buttock [see Warnings and Precautions ( 5.1 )] .

to the deep tissue with subcutaneous or intramuscular injection. While cleansing with alcohol may reduce the presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the risk of Clostridium infection, do not inject AUVI-Q 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 Risk 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, 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 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 )] . Epinephrine can temporarily exacerbate the underlying conditions 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 AUVI-Q 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 AUVI-Q should not deter administration of the drug for treatment of serious allergic or other emergency situations.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Injection-Related Complications [see Warnings and Precautions ( 5.1 )] Serious Infections at the Injection Site [see Warnings and Precautions ( 5.2 )] Risks Associated with Use of Epinephrine in Certain Coexisting Conditions [see Warnings and Precautions ( 5.3 )] Allergic Reactions Associated with Sulfite [see Warnings and Precautions ( 5.4 )] Adverse Reactions from Postapproval Use of Epinephrine Products The following adverse reactions have been identified during postapproval use of epinephrine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: angina, arrhythmias (including fatal ventricular fibrillation), cerebral hemorrhage, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy, and stress cardiomyopathy Gastrointestinal Disorders: nausea, vomiting Infections: Clostridial infections (gas gangrene) Metabolism and Nutrition Disorders: transient hyperglycemia, sweating Neurological: disorientation, impaired memory, panic, psychomotor agitations, sleepiness, tingling, weakness, hypoesthesia, dizziness, tremor, headache Psychiatric: anxiety, apprehensiveness, restlessness Respiratory: respiratory difficulties Skin and Subcutaneous Tissue Disorders: bruising, bleeding, discoloration, erythema, necrotizing fasciitis, myonecrosis Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact kaleo, Inc. at 1-877-302-8847 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

7 DRUG INTERACTIONS Cardiac glycosides, diuretics, or anti-arrhythmics: observe for development of cardiac arrhythmias. ( 7.1 ) Tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, certain antihistamines, and catechol-O-methyl transferase inhibitors may potentiate effects of epinephrine. ( 7.2 ) Beta-adrenergic blocking drugs antagonize cardiostimulating and bronchodilating effects of epinephrine. ( 7.3 ) Alpha-adrenergic blocking drugs antagonize vasoconstricting and hypertensive effects of epinephrine. ( 7.3 ) Ergot alkaloids may reverse the pressor effects of epinephrine. ( 7.3 ) 7.1 Drugs Increasing Risk of Cardiac Arrhythmias Observe patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics for the development of cardiac arrhythmias [see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6 )] . 7.2 Drugs Potentiating Effects of Epinephrine The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine, and catechol-O-methyl transferase (COMT) inhibitors such as entacapone. 7.3 Drugs Antagonizing Effects of Epinephrine The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta- adrenergic blocking drugs, such as propranolol. The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha- adrenergic blocking drugs, such as phentolamine. Ergot alkaloids may also reverse the pressor effects of epinephrine.

8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 8.5 ) 8.1 Pregnancy Risk Summary Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with anaphylaxis. Epinephrine is first-line treatment of anaphylaxis and should not be delayed (see Clinical Considerations ) . In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. Treatment of anaphylaxis during pregnancy should not be delayed. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days). 8.2 Lactation Risk Summary There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. However, due to its poor oral bioavailability and short half-life, transfer of epinephrine into breastmilk is expected to be low. Treatment of anaphylaxis in breastfeeding patients should not be delayed. 8.4 Pediatric Use The safety and effectiveness of AUVI-Q for the emergency treatment of type I allergic reactions, including anaphylaxis have been established in pediatric patients who weigh 7.5 kg or greater. The use of AUVI-Q for this indication is supported by clinical experience.

ing patients should not be delayed. 8.4 Pediatric Use The safety and effectiveness of AUVI-Q for the emergency treatment of type I allergic reactions, including anaphylaxis have been established in pediatric patients who weigh 7.5 kg or greater. The use of AUVI-Q for this indication is supported by clinical experience. Clinical experience with the use of epinephrine suggests that the adverse reactions seen in pediatric patients are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from AUVI-Q are fixed, use other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary. The safety and effectiveness of AUVI-Q have not been established in pediatric patients who weigh less than 7.5 kg. 8.5 Geriatric Use Clinical studies of AUVI-Q for emergency treatment of type I allergic reactions, including anaphylaxis, were not conducted to determine whether they respond differently from younger patients. However, other reported clinical experience with use of epinephrine for treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, these patients may be at greater risk for developing adverse reactions after epinephrine administration [see Overdosage ( 10 )] .

8.1 Pregnancy Risk Summary Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with anaphylaxis. Epinephrine is first-line treatment of anaphylaxis and should not be delayed (see Clinical Considerations ) . In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. Treatment of anaphylaxis during pregnancy should not be delayed. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days).

8.4 Pediatric Use The safety and effectiveness of AUVI-Q for the emergency treatment of type I allergic reactions, including anaphylaxis have been established in pediatric patients who weigh 7.5 kg or greater. The use of AUVI-Q for this indication is supported by clinical experience. Clinical experience with the use of epinephrine suggests that the adverse reactions seen in pediatric patients are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from AUVI-Q are fixed, use other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary. The safety and effectiveness of AUVI-Q have not been established in pediatric patients who weigh less than 7.5 kg.

8.5 Geriatric Use Clinical studies of AUVI-Q for emergency treatment of type I allergic reactions, including anaphylaxis, were not conducted to determine whether they respond differently from younger patients. However, other reported clinical experience with use of epinephrine for treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, these patients may be at greater risk for developing adverse reactions after epinephrine administration [see Overdosage ( 10 )] .

10 OVERDOSAGE Overdosage of epinephrine has been reported to produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia, which may be accompanied by fatal cardiac arrhythmias; premature ventricular contractions followed by multifocal ventricular tachycardia; atrial tachycardia and occasionally by atrioventricular block; extreme pallor and coldness of the skin; metabolic acidosis; kidney failure. Epinephrine is rapidly inactivated in the body and treatment following overdosage with epinephrine is primarily supportive. Treatment of epinephrine associated pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of epinephrine associated arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

11 DESCRIPTION AUVI-Q (epinephrine injection, USP) 0.3 mg, 0.15 mg and 0.1 mg is an autoinjector and a combination product containing drug and device components. AUVI-Q includes audible (electronic voice instructions, beeps) and visible (LED lights) cues for use. The needle automatically retracts after the injection is complete. Each AUVI-Q 0.3 mg delivers a single dose of 0.3 mg epinephrine from epinephrine injection, USP (0.3 mL) in a sterile solution. Each AUVI-Q 0.15 mg delivers a single dose of 0.15 mg epinephrine from epinephrine injection, USP (0.15 mL) in a sterile solution. Each AUVI-Q 0.1 mg delivers a single dose of 0.1 mg epinephrine from epinephrine injection, USP (0.1 mL) in a sterile solution. AUVI-Q 0.3 mg, AUVI-Q 0.15 mg and AUVI-Q 0.1 mg each contain 0.76 mL epinephrine solution. 0.3 mL, 0.15 mL and 0.1 mL epinephrine solution is dispensed for AUVI-Q 0.3 mg, AUVI-Q 0.15 mg and AUVI-Q 0.1 mg, respectively, when activated. The remaining solution is not available for future use and should be discarded. Each 0.3 mL in AUVI-Q 0.3 mg contains 0.3 mg epinephrine, 2.3 mg sodium chloride, 0.45 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2– 5.0. Each 0.15 mL in AUVI-Q 0.15 mg contains 0.15 mg epinephrine, 1.2 mg sodium chloride, 0.225 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2–5.0. Each 0.1 mL in AUVI-Q 0.1 mg contains 0.1 mg epinephrine, 0.78 mg sodium chloride, 0.15 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2–5.0. Epinephrine is a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4-Dihydroxy-a-[(methylamino)methyl]benzyl alcohol with the following structure: Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. AUVI-Q is not made with natural rubber latex. AUVI-Q instructional and safety systems should be thoroughly reviewed with patients and caregivers prior to use [see Patient Counseling Information ( 17 )] . Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha and beta-adrenergic receptors. Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. 12.2 Pharmacodynamics When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

12.1 Mechanism of Action Epinephrine acts on both alpha and beta-adrenergic receptors. Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage ( 1 )] . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage ( 1 )] . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied AUVI-Q (epinephrine injection) is a clear and colorless solution for intramuscular or subcutaneous use. AUVI-Q is available as an autoinjector as described in Table 2 . Table 2. AUVI-Q Autoinjector Package Configurations and Strengths Package Configuration Strength National Drug Code (NDC) 2 autoinjectors 0.3 mg/0.3 mL NDC 60842-023-02 2 autoinjectors 0.15 mg/0.15 mL NDC 60842-022-02 2 autoinjectors 0.1 mg/0.1 mL NDC 60842-021-02 Storage and Handling Protect from light. Epinephrine is light sensitive and should be stored in the outer case. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Do not freeze. Before using, check to make sure the solution in the autoinjector is clear and colorless. Replace the autoinjector if the solution is discolored, cloudy, or contains particles.

<table width="750" styleCode="Noautorules"><col width="34%" align="center"/><col width="32%" align="center"/><col width="34%" align="center"/><tbody valign="top"><tr><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Package Configuration</content></td><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Strength</content></td><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">National Drug Code (NDC)</content></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.3 mg/0.3 mL</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-023-02</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.15 mg/0.15 mL</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-022-02</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.1 mg/0.1 mL</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-021-02</td></tr></tbody></table>

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Administration and Training Instruct patients and/or caregivers in the appropriate use of AUVI-Q. AUVI-Q should be injected into the middle of the outer thigh (through clothing, if necessary). Each device is a single-dose injection. Advise patients and/or caregivers when to seek emergency medical care for close monitoring of the type I allergic emergency and in the event that further treatment is required. Instruct patients and/or caregivers to inspect the epinephrine solution visually through the viewing window periodically. AUVI-Q should be replaced if the epinephrine solution appears discolored, cloudy, or contains particles. Instruct caregivers to hold the leg of young children or infants firmly in place and limit movement prior to and during injection [see Warnings and Precautions ( 5.1 )] . Instruct patients and/or caregivers that the needle will not be visible after the injection and they may not feel the injection when it occurs. Instruct patients and/or caregivers that AUVI-Q includes a 2- second countdown after it is activated and then the voice instructions will indicate when the injection has been completed and to seek medical care, if needed. Instruct patients that AUVI-Q’s black base will lock up onto the device housing and the lights will blink red after the injection has been completed. These post-use indicators help patients and/or caregivers know that AUVI-Q has been activated and an epinephrine injection has been administered. Instruct patients and/or caregivers to use and practice with the Trainer to familiarize themselves with the use of AUVI-Q in an allergic emergency. The Trainer may be used multiple times. Injection-Related Complications Advise patients to seek immediate medical care in the case of accidental injection into the digits, hands, or feet because such an accidental injection to these areas may cause loss of blood flow to the affected area [see Warnings and Precautions ( 5.1 )] . Serious Infections at the Injection Site Advise patients that 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. Instruct 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 [see Warnings and Precautions ( 5.2 )] . Risks Associated with Certain Coexisting Conditions Advise patients with coexisting conditions (cardiac arrhythmia and ischemia, hypertension, pulmonary edema, hyperthyroidism, renal impairment, Parkinson’s disease, diabetes), for increased risks that may be associated with use of epinephrine [see Warnings and Precautions ( 5.3 )] . Storage and Handling Epinephrine is light sensitive and should be stored in the outer case provided to protect it from light. Instruct patients that AUVI-Q must be used or properly disposed once the red safety guard is removed [see How Supplied/Storage and Handling ( 16 )] . Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO ® and AUVI-Q ® are registered trademarks of kaleo, Inc. © 2025 kaleo, Inc.

y guard is removed [see How Supplied/Storage and Handling ( 16 )] . Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO ® and AUVI-Q ® are registered trademarks of kaleo, Inc. © 2025 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate

PATIENT INFORMATION AUVI-Q® [Aw-Vee-Kyoo] (epinephrine injection) For intramuscular or subcutaneous use For allergic emergencies (anaphylaxis) Read this Patient Information leaflet before you have to use AUVI-Q and each time you get a refill. There may be new information. You, your caregiver, or others who may be in a position to administer AUVI-Q should know how to use it before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about AUVI-Q? Always carry AUVI-Q with you because you may not know when a life-threatening allergic reaction (anaphylactic reaction) may happen. Talk to your healthcare provider if you need additional units to keep at work, school, etc. An anaphylactic reaction is a life-threatening allergic reaction that can happen within minutes and can be caused by stinging and biting insects (bees, wasps, hornets, and mosquitoes), allergy shots, foods, medicines, exercise, or other unknown causes. Follow your healthcare provider’s instructions on when to use AUVI-Q if you have the symptoms of an anaphylactic reaction, which may include the symptoms listed below: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements dizziness or fainting Tell your family members and others where you keep AUVI-Q and how to use it before you need it. You may be unable to speak in an allergic emergency. Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q. Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help. What is AUVI-Q? AUVI-Q is a prescription medicine used to treat life-threatening allergic reactions including anaphylaxis in adults and children who weigh 16.5 pounds (7.5 kilograms) or more who are at risk for or have a history of serious allergic reactions. AUVI-Q is for immediate self (or caregiver) administration. It is not known if AUVI-Q is safe and effective in children who weigh less than 16.5 pounds (7.5 kilograms). What should I tell my healthcare provider before using AUVI-Q? Before using AUVI-Q, tell your healthcare provider about all of your medical conditions, especially if you: have heart problems or high blood pressure. have diabetes. have thyroid problems. have kidney problems. have history of depression. have Parkinson’s disease. are pregnant or plan to become pregnant. It is not known if AUVI-Q will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if AUVI-Q passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. AUVI-Q and other medicines may affect each other, causing side effects. AUVI-Q may affect the way other medicines work, and other medicines may affect how AUVI-Q works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use AUVI-Q?

AUVI-Q and other medicines may affect each other, causing side effects. AUVI-Q may affect the way other medicines work, and other medicines may affect how AUVI-Q works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use AUVI-Q? Read the Instructions for Use at the end of this Patient Information leaflet for information about the right way to use AUVI-Q. Use AUVI-Q exactly as your healthcare providers tells you to use it. AUVI-Q should only be injected into your outer thigh. If needed, AUVI-Q can be injected through your clothing. Each AUVI-Q contains only 1 dose of medicine. If a second dose of AUVI-Q is needed, it should be given starting 5 minutes after the first dose. You should always carry 2 AUVI-Q devices with you. If you need more than 2 doses of epinephrine for a single anaphylaxis episode, more doses must be given by a healthcare provider. You may request a Trainer for AUVI-Q. Additional training resources are available at www.auvi-q.com . Practice with the Trainer for AUVI-Q before an allergic emergency happens to familiarize yourself with the use of AUVI-Q in an allergic emergency. The Trainer for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection. If you take too much AUVI-Q, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are the possible side effects of AUVI-Q? AUVI-Q may cause serious side effects. AUVI-Q should only be injected into your outer thigh. Do not inject AUVI-Q into your: veins buttocks fingers, toes, hands or feet If you accidentally inject AUVI-Q into any other part of your body, go to the nearest hospital emergency room right away. Tell the healthcare provider where on your body you received the accidental injection. Rarely, patients who use AUVI-Q may develop infections at the injection site within a few days of an injection. Some of these infections can be serious. Call your healthcare provider right away if you have any of the following at an injection site: redness that does not go away swelling tenderness the area feels warm to the touch If you inject a young child or infant with AUVI-Q, hold their leg firmly in place before and during the injection to prevent injuries. Ask your healthcare provider to show you how to properly hold the leg of a young child or infant during an injection. If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have more or longer lasting side effects when you use AUVI-Q. Talk to your healthcare provider about all your medical conditions. Common side effects of AUVI-Q include: fast, irregular, or ‘pounding’ heart beat sweating shakiness headache paleness feelings of over excitement, nervousness, or anxiety weakness dizziness nausea and vomiting breathing problems Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of AUVI-Q. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store AUVI-Q? Store AUVI-Q at room temperature between 68° to 77°F (20° to 25°C). Do not freeze. Do not expose to extreme heat or cold. For example, do not store in your vehicle’s glove box. Before using, examine contents in the viewing window. Solution should be clear. If the solution is discolored, cloudy or contains solid particles, replace the autoinjector. Your AUVI-Q has an expiration date. Replace it before the expiration date. Keep AUVI-Q in the outer case it comes in to protect it from light.

box. Before using, examine contents in the viewing window. Solution should be clear. If the solution is discolored, cloudy or contains solid particles, replace the autoinjector. Your AUVI-Q has an expiration date. Replace it before the expiration date. Keep AUVI-Q in the outer case it comes in to protect it from light. Keep AUVI-Q and all medicines out of the reach of children. General information about the safe and effective use of AUVI-Q. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use AUVI-Q for a condition for which it was not prescribed. Do not give AUVI-Q to other people, even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about AUVI-Q. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about AUVI-Q that is written for health professionals. What are the ingredients in AUVI-Q? Active ingredient: epinephrine. Inactive Ingredients: sodium chloride, sodium bisulfite, hydrochloric acid, and water. AUVI-Q does not contain latex. For more information and video instructions on the use of AUVI-Q, go to www.auvi-q.com or call 1-877-302-8847. Instructions for Use Read this Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Ask your healthcare provider to show you how to properly hold the leg in place while administering a dose. Automated Voice Instructions AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency. How to use your AUVI-Q Figure A. 1. Pull AUVI-Q up from the outer case. See Figure B . Do not go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. Figure B. 2. Pull Red safety guard down and off of AUVI-Q. See Figure C . To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. Note: The red safety guard is made to fit tight. Pull firmly to remove. Figure C. 3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . Only inject into the middle of the outer thigh. Do not inject into any other part of the body. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place while administering an injection See Figure E . Figure D. (For AUVI-Q 0.3 mg and AUVI-Q 0.15 mg) Figure E. (For AUVI-Q 0.1 mg) Note: AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is normal and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. The needle automatically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek medical care if needed. AUVI-Q will beep, and the lights will blink red. 4.

tically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek medical care if needed. AUVI-Q will beep, and the lights will blink red. 4. Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q. Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help. Replace the outer case and talk to your healthcare provider about the right way to throw away your AUVI-Q. Ask your healthcare provider for an AUVI-Q prescription refill. After the use of AUVI-Q: The black base will lock into place. The voice instruction system will say “seek medical care if needed”, say “this AUVI-Q has been used…”, and the lights will blink red. Do not replace the red safety guard. The viewing window will no longer be clear. It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q. AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed after the red safety guard is removed. Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed. This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: Apr 2025 Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2025 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate Figure A Figure B Figure C Figure D Figure E

<table width="100%" styleCode="Noautorules"><col width="100%" align="left"/><tbody><tr><td align="center" styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">PATIENT INFORMATION</content></paragraph><paragraph>AUVI-Q&#xAE; [Aw-Vee-Kyoo] (epinephrine injection) For intramuscular or subcutaneous use For allergic emergencies (anaphylaxis)</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph>Read this Patient Information leaflet before you have to use AUVI-Q and each time you get a refill. There may be new information. You, your caregiver, or others who may be in a position to administer AUVI-Q should know how to use it before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What is the most important information I should know about AUVI-Q?</content></paragraph><list listType="ordered" styleCode="Arabic"><item>Always carry AUVI-Q with you because you may not know when a life-threatening allergic reaction (anaphylactic reaction) may happen. Talk to your healthcare provider if you need additional units to keep at work, school, etc. An anaphylactic reaction is a life-threatening allergic reaction that can happen within minutes and can be caused by stinging and biting insects (bees, wasps, hornets, and mosquitoes), allergy shots, foods, medicines, exercise, or other unknown causes. Follow your healthcare provider&#x2019;s instructions on when to use AUVI-Q if you have the symptoms of an anaphylactic reaction, which may include the symptoms listed below: <list listType="unordered" styleCode="Disc"><item>trouble breathing</item><item>wheezing</item><item>hoarseness (changes in the way your voice sounds)</item><item>hives (raised reddened rash that may itch)</item><item>severe itching</item><item>swelling of your face, lips, mouth or tongue</item><item>skin rash, redness, or swelling</item><item>fast heartbeat</item><item>weak pulse</item><item>feeling very anxious</item><item>confusion</item><item>stomach pain</item><item>losing control of urine or bowel movements</item><item>dizziness or fainting</item></list></item><item>Tell your family members and others where you keep AUVI-Q and how to use it before you need it. You may be unable to speak in an allergic emergency.</item><item>Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q. Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help.</item></list></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What is AUVI-Q?</content></paragraph><list listType="unordered" styleCode="Disc"><item>AUVI-Q is a prescription medicine used to treat life-threatening allergic reactions including anaphylaxis in adults and children who weigh 16.5 pounds (7.5 kilograms) or more who are at risk for or have a history of serious allergic reactions.</item><item>AUVI-Q is for immediate self (or caregiver) administration.</item></list><paragraph>It is not known if AUVI-Q is safe and effective in children who weigh less than 16.5 pounds (7.5 kilograms).</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What should I tell my healthcare provider before using AUVI-Q?

r) administration.</item></list><paragraph>It is not known if AUVI-Q is safe and effective in children who weigh less than 16.5 pounds (7.5 kilograms).</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What should I tell my healthcare provider before using AUVI-Q? Before using AUVI-Q, tell your healthcare provider about all of your medical conditions, especially if you:</content></paragraph><list listType="unordered" styleCode="Disc"><item>have heart problems or high blood pressure.</item><item>have diabetes. </item><item>have thyroid problems.</item><item>have kidney problems.</item><item>have history of depression. </item><item>have Parkinson&#x2019;s disease.</item><item>are pregnant or plan to become pregnant. It is not known if AUVI-Q will harm your unborn baby.</item><item>are breastfeeding or plan to breastfeed. It is not known if AUVI-Q passes into your breast milk. </item></list><paragraph><content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content> including prescription and non-prescription medicines, vitamins, and herbal supplements. </paragraph><paragraph>AUVI-Q and other medicines may affect each other, causing side effects. AUVI-Q may affect the way other medicines work, and other medicines may affect how AUVI-Q works. </paragraph><paragraph>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">How should I use AUVI-Q? </content></paragraph><list listType="unordered" styleCode="Disc"><item>Read the Instructions for Use at the end of this Patient Information leaflet for information about the right way to use AUVI-Q.</item><item>Use AUVI-Q exactly as your healthcare providers tells you to use it.</item><item>AUVI-Q should only be injected into your outer thigh. If needed, AUVI-Q can be injected through your clothing.</item><item>Each AUVI-Q contains only 1 dose of medicine.</item><item>If a second dose of AUVI-Q is needed, it should be given starting 5 minutes after the first dose.</item><item>You should always carry 2 AUVI-Q devices with you.</item><item>If you need more than 2 doses of epinephrine for a single anaphylaxis episode, more doses must be given by a healthcare provider.</item><item>You may request a Trainer for AUVI-Q. Additional training resources are available at <linkHtml href="https://www.auvi-q.com">www.auvi-q.com</linkHtml>. <list listType="unordered" styleCode="Circle"><item>Practice with the Trainer for AUVI-Q before an allergic emergency happens to familiarize yourself with the use of AUVI-Q in an allergic emergency.</item><item>The Trainer for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection.</item></list></item><item>If you take too much AUVI-Q, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</item></list></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What are the possible side effects of AUVI-Q?</content></paragraph><paragraph><content styleCode="bold">AUVI-Q may cause serious side effects.</content></paragraph><list listType="unordered" styleCode="Disc"><item><content styleCode="bold">AUVI-Q should only be injected into your outer thigh. Do not</content> inject AUVI-Q into your: <list listType="unordered" styleCode="Circle"><item>veins</item><item>buttocks</item><item>fingers, toes, hands or feet</item></list> If you accidentally inject AUVI-Q into any other part of your body, go to the nearest hospital emergency room right away.

into your outer thigh. Do not</content> inject AUVI-Q into your: <list listType="unordered" styleCode="Circle"><item>veins</item><item>buttocks</item><item>fingers, toes, hands or feet</item></list> If you accidentally inject AUVI-Q into any other part of your body, go to the nearest hospital emergency room right away. Tell the healthcare provider where on your body you received the accidental injection. </item></list><list listType="unordered" styleCode="Disc"><item>Rarely, patients who use AUVI-Q may develop infections at the injection site within a few days of an injection. Some of these infections can be serious. Call your healthcare provider right away if you have any of the following at an injection site: <list listType="unordered" styleCode="Circle"><item>redness that does not go away</item><item>swelling</item><item>tenderness</item><item>the area feels warm to the touch</item></list></item><item>If you inject a young child or infant with AUVI-Q, hold their leg firmly in place before and during the injection to prevent injuries. Ask your healthcare provider to show you how to properly hold the leg of a young child or infant during an injection. </item><item><content styleCode="bold">If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have more or longer lasting side effects when you use AUVI-Q. Talk to your healthcare provider about all your medical conditions.</content></item></list><paragraph>Common side effects of AUVI-Q include:</paragraph><list listType="unordered" styleCode="Disc"><item>fast, irregular, or &#x2018;pounding&#x2019; heart beat </item><item>sweating</item><item>shakiness</item><item>headache</item><item>paleness</item><item>feelings of over excitement, nervousness, or anxiety</item><item>weakness</item><item>dizziness</item><item>nausea and vomiting</item><item>breathing problems </item></list><paragraph>Tell your healthcare provider if you have any side effect that bothers you or that does not go away. </paragraph><paragraph>These are not all of the possible side effects of AUVI-Q. For more information, ask your healthcare provider or pharmacist. </paragraph><paragraph>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">How should I store AUVI-Q? </content></paragraph><list listType="unordered" styleCode="Disc"><item>Store AUVI-Q at room temperature between 68&#xB0; to 77&#xB0;F (20&#xB0; to 25&#xB0;C). </item><item><content styleCode="bold">Do not</content> freeze. <content styleCode="bold">Do not</content> expose to extreme heat or cold. For example, <content styleCode="bold">do not</content> store in your vehicle&#x2019;s glove box. </item><item>Before using, examine contents in the viewing window. Solution should be clear. If the solution is discolored, cloudy or contains solid particles, replace the autoinjector.</item><item>Your AUVI-Q has an expiration date. Replace it before the expiration date.</item><item>Keep AUVI-Q in the outer case it comes in to protect it from light.</item></list><paragraph><content styleCode="bold">Keep AUVI-Q and all medicines out of the reach of children.</content></paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">General information about the safe and effective use of AUVI-Q.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use AUVI-Q for a condition for which it was not prescribed. Do not give AUVI-Q to other people, even if they have the same symptoms that you have.

and effective use of AUVI-Q.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use AUVI-Q for a condition for which it was not prescribed. Do not give AUVI-Q to other people, even if they have the same symptoms that you have. It may harm them.</paragraph><paragraph>This Patient Information leaflet summarizes the most important information about AUVI-Q. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about AUVI-Q that is written for health professionals.</paragraph></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule"><paragraph><content styleCode="bold">What are the ingredients in AUVI-Q? Active ingredient:</content> epinephrine. <content styleCode="bold">Inactive Ingredients:</content> sodium chloride, sodium bisulfite, hydrochloric acid, and water.</paragraph><paragraph>AUVI-Q does not contain latex.</paragraph><paragraph>For more information and video instructions on the use of AUVI-Q, go to www.auvi-q.com or call 1-877-302-8847.</paragraph></td></tr></tbody></table>

Inactive Ingredients:</content> sodium chloride, sodium bisulfite, hydrochloric acid, and water.</paragraph><paragraph>AUVI-Q does not contain latex.</paragraph><paragraph>For more information and video instructions on the use of AUVI-Q, go to www.auvi-q.com or call 1-877-302-8847.</paragraph></td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="100%" align="left"/><tbody><tr><td align="center"><paragraph><content styleCode="bold">Instructions for Use</content></paragraph></td></tr><tr><td><paragraph>Read this Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. </paragraph><paragraph>If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Ask your healthcare provider to show you how to properly hold the leg in place while administering a dose.</paragraph><paragraph><content styleCode="bold">Automated Voice Instructions</content></paragraph><paragraph>AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency.</paragraph><paragraph><content styleCode="bold">How to use your AUVI-Q</content></paragraph><paragraph><content styleCode="bold">Figure A.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM164"/></paragraph><paragraph><content styleCode="bold">1. Pull AUVI-Q up from the outer case. See <linkHtml href="#figureb">Figure B</linkHtml>. Do not</content> go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. </paragraph><paragraph ID="figureb"><content styleCode="bold">Figure B.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM165"/></paragraph><paragraph><content styleCode="bold">2. Pull Red safety guard down and off of AUVI-Q. See <linkHtml href="#figurec">Figure C</linkHtml>.</content> To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. </paragraph><paragraph><content styleCode="bold">Note:</content> The red safety guard is made to fit tight. <content styleCode="bold">Pull firmly to remove.</content></paragraph><paragraph ID="figurec"><content styleCode="bold">Figure C.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM166"/></paragraph><paragraph><content styleCode="bold">3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See <linkHtml href="#figured">Figure D</linkHtml>. </content></paragraph><paragraph><content styleCode="bold">Only</content> inject into the middle of the outer thigh. <content styleCode="bold">Do not</content> inject into any other part of the body.

til you hear a click and hiss sound, and hold in place for 2 seconds. See <linkHtml href="#figured">Figure D</linkHtml>. </content></paragraph><paragraph><content styleCode="bold">Only</content> inject into the middle of the outer thigh. <content styleCode="bold">Do not</content> inject into any other part of the body. </paragraph><paragraph><content styleCode="bold">If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place while administering an injection See <linkHtml href="#figuree">Figure E</linkHtml>.</content></paragraph><paragraph ID="figured"><content styleCode="bold">Figure D.</content></paragraph><paragraph><content styleCode="bold">(For AUVI-Q 0.3 mg and AUVI-Q 0.15 mg)</content></paragraph><paragraph><renderMultiMedia referencedObject="MM167"/></paragraph><paragraph ID="figuree"><content styleCode="bold">Figure E.</content></paragraph><paragraph><content styleCode="bold">(For AUVI-Q 0.1 mg)</content></paragraph><paragraph><renderMultiMedia referencedObject="MM189"/></paragraph><paragraph><content styleCode="bold">Note:</content> AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is normal and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound.</paragraph><paragraph>The needle automatically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek medical care if needed. AUVI-Q will beep, and the lights will blink red.</paragraph><paragraph><content styleCode="bold">4. Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q.</content></paragraph><paragraph><content styleCode="bold">Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help.</content></paragraph><paragraph><content styleCode="bold">Replace the outer case and talk to your healthcare provider about the right way to throw away your AUVI-Q.</content></paragraph><paragraph><content styleCode="bold">Ask your healthcare provider for an AUVI-Q prescription refill. After the use of AUVI-Q: </content></paragraph><list listType="unordered" styleCode="Disc"><item>The black base will lock into place.</item><item>The voice instruction system will say &#x201C;seek medical care if needed&#x201D;, say &#x201C;this AUVI-Q has been used&#x2026;&#x201D;, and the lights will blink red. </item><item>Do not replace the red safety guard. </item><item>The viewing window will no longer be clear. </item><item>It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. </item><item>Talk to your healthcare provider about the right way to throw away your AUVI-Q. </item><item>AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed after the red safety guard is removed. </item></list><paragraph>Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed.</paragraph><paragraph>This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration</paragraph> <paragraph>Revised: Apr 2025</paragraph> <paragraph>Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KAL&#xC9;O&#xAE; and AUVI-Q&#xAE; are registered trademarks of kaleo, Inc.

istration</paragraph> <paragraph>Revised: Apr 2025</paragraph> <paragraph>Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KAL&#xC9;O&#xAE; and AUVI-Q&#xAE; are registered trademarks of kaleo, Inc. &#xA9; 2025 kaleo, Inc.</paragraph> <paragraph><content styleCode="bold">*For California Only: This product uses batteries containing Perchlorate Material &#x2013; special handling may apply. See <linkHtml href="https://www.dtsc.ca.gov/hazardouswaste/perchlorate">www.dtsc.ca.gov/hazardouswaste/perchlorate</linkHtml></content></paragraph> </td></tr></tbody></table>

Instructions for Use Read this Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Ask your healthcare provider to show you how to properly hold the leg in place while administering a dose. Automated Voice Instructions AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency. How to use your AUVI-Q Figure A. 1. Pull AUVI-Q up from the outer case. See Figure B . Do not go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. Figure B. 2. Pull Red safety guard down and off of AUVI-Q. See Figure C . To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. Note: The red safety guard is made to fit tight. Pull firmly to remove. Figure C. 3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . Only inject into the middle of the outer thigh. Do not inject into any other part of the body. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place while administering an injection See Figure E . Figure D. (For AUVI-Q 0.3 mg and AUVI-Q 0.15 mg) Figure E. (For AUVI-Q 0.1 mg) Note: AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is normal and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. The needle automatically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek medical care if needed. AUVI-Q will beep, and the lights will blink red. 4. Get medical care for further treatment of the allergic emergency if needed after using AUVI-Q. Before you receive AUVI-Q, your healthcare provider should talk to you about when to get emergency help. Replace the outer case and talk to your healthcare provider about the right way to throw away your AUVI-Q. Ask your healthcare provider for an AUVI-Q prescription refill. After the use of AUVI-Q: The black base will lock into place. The voice instruction system will say “seek medical care if needed”, say “this AUVI-Q has been used…”, and the lights will blink red. Do not replace the red safety guard. The viewing window will no longer be clear. It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q. AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed after the red safety guard is removed.

is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q. AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed after the red safety guard is removed. Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed. This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: Apr 2025 Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2025 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate

<table width="100%" styleCode="Noautorules"><col width="100%" align="left"/><tbody><tr><td align="center"><paragraph><content styleCode="bold">Instructions for Use</content></paragraph></td></tr><tr><td><paragraph>Read this Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. </paragraph><paragraph>If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Ask your healthcare provider to show you how to properly hold the leg in place while administering a dose.</paragraph><paragraph><content styleCode="bold">Automated Voice Instructions</content></paragraph><paragraph>AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency.</paragraph><paragraph><content styleCode="bold">How to use your AUVI-Q</content></paragraph><paragraph><content styleCode="bold">Figure A.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM164"/></paragraph><paragraph><content styleCode="bold">1. Pull AUVI-Q up from the outer case. See <linkHtml href="#figureb">Figure B</linkHtml>. Do not</content> go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. </paragraph><paragraph ID="figureb"><content styleCode="bold">Figure B.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM165"/></paragraph><paragraph><content styleCode="bold">2. Pull Red safety guard down and off of AUVI-Q. See <linkHtml href="#figurec">Figure C</linkHtml>.</content> To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. </paragraph><paragraph><content styleCode="bold">Note:</content> The red safety guard is made to fit tight. <content styleCode="bold">Pull firmly to remove.</content></paragraph><paragraph ID="figurec"><content styleCode="bold">Figure C.</content></paragraph><paragraph><renderMultiMedia referencedObject="MM166"/></paragraph><paragraph><content styleCode="bold">3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See <linkHtml href="#figured">Figure D</linkHtml>. </content></paragraph><paragraph><content styleCode="bold">Only</content> inject into the middle of the outer thigh. <content styleCode="bold">Do not</content> inject into any other part of the body.

TRAINER FOR AUVI-Q® Trainer Instructions for Use Important: The TRAINER for AUVI-Q Does Not contain a needle or medicine. In case of an allergic emergency, use the real AUVI-Q and not the gray Trainer. Always carry your real Auvi-Q with you in case of an allergic emergency. Important Information about the TRAINER for AUVI-Q: Inside your TRAINER for AUVI-Q are: batteries a speaker that will make a beeping sound and that produces electronic voice instructions red and green blinking lights The TRAINER for AUVI-Q batteries are made to last long enough for you to practice 1 time each day for 2 years. If your TRAINER for AUVI-Q does not work properly call your healthcare provider for a new Trainer. What is the TRAINER for AUVI-Q? The TRAINER for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection. Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency. Your TRAINER for AUVI-Q Figure A TRAINER for AUVI-Q Top view AUVI-Q AUVI-Q 0.3 mg is orange AUVI-Q 0.15 mg is blue AUVI-Q 0.1 mg is white and lavender TRAINER for AUVI-Q: is inside a gray outer case does not have a needle or medicine inside can be reused (the red safety guard can be placed back on the base of the Trainer after use) has no expiration date has embossed “TRAINER” on top of the device AUVI-Q: is inside an orange (0.3 mg) or blue (0.15 mg) or white and lavender (0.1 mg) outer case contains a needle and epinephrine medicine cannot be reused (AUVI-Q must be used or properly disposed once the red safety guard is removed) has a medicine expiration date listed on the device In case of an allergic emergency, use the real AUVI-Q and not the gray Trainer. Who should practice using the TRAINER for AUVI-Q? Anyone who may need to help you with AUVI-Q in case of an allergic emergency: You Caregivers Family Friends Co-workers Teachers Child Care or Day Care Workers Have them practice using the Trainer and review the Patient Information Leaflet included in the packaging with each prescription of AUVI-Q. For more information and video instructions on the use of AUVI -Q, go to www.AUVI-Q.com or call 1-877-302-8847. Practicing with the TRAINER for AUVI-Q Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency. You should practice daily for the first week after you receive your TRAINER for AUVI-Q to help you feel comfortable using AUVI-Q quickly and safely. Even when you are comfortable using the Trainer, continue to practice using it often. How to Use the Trainer How the TRAINER for AUVI-Q works Although the Trainer does not have a needle and contains no medicine, it works the same way as the real AUVI-Q. As with the real AUVI-Q, the TRAINER for AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for the TRAINER for AUVI-Q for any reason, you can still use the TRAINER for AUVI-Q as instructed in this leaflet to practice. The TRAINER for AUVI-Q has the same blinking red and green lights as the real AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens.

and green lights as the real AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. Follow These Steps 1.Pull the TRAINER for AUVI-Q from the outer case. See Figure B 2. Pull Red safety guard down and off of the Trainer. See Figure C . Figure B Figure C Note: The red safety guard is made to fit tight similar to the safety guard on the real AUVI-Q. Pull firmly to remove. 3. Place black end against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. (See Figure E ). Figure D Figure E Note: In an actual emergency, after the injection you would seek medical care if needed. Only practice using the middle of your outer thigh. The outer thigh is where you would inject with the real AUVI-Q. Note: The TRAINER for AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is the same sound that is made with the real AUVI-Q. This is normal, and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. 4. After practicing, reset the TRAINER for AUVI-Q: a. Replace the Red safety guard. Do not hold the black base while inserting the Red safety guard. The Black base will drop down into its original location during Red safety guard insertion. See Figure F . b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system. See Figure G . Figure F Figure G Note: Leave the TRAINER for AUVI-Q in its outer case for at least 5 seconds between each time you practice to allow the electronic voice system to reset. Storage: Store the TRAINER for AUVI-Q at room temperature; the TRAINER for AUVI-Q should not be used at temperatures less than 50°F (10°C) or greater than 104°F (40°C). Store the TRAINER for AUVI-Q in its outer case. Keep the TRAINER for AUVI-Q away from dirt, chemicals, and water. Disposal: The TRAINER for AUVI-Q contains electronics and lithium coin cell batteries, and should be disposed of in the correct manner. Follow your State and local environmental regulations for disposal. For California Only: This product uses batteries containing Perchlorate Material - special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2025 kaleo, Inc. Rev. Apr 2025 Figure A1 Figure A2 Figure A3 Figure A4 Figure A5 Figure B Figure C Figure D Figure E Figure F Figure G

<table width="100%" styleCode="Noautorules"><col width="100%" align="left"/><tbody><tr><td align="center"><paragraph><content styleCode="bold">TRAINER FOR AUVI-Q&#xAE; Trainer Instructions for Use</content></paragraph></td></tr><tr><td><paragraph><content styleCode="bold underline">Important: </content> <content styleCode="bold underline">The TRAINER for AUVI-Q Does Not contain a needle or medicine.</content></paragraph> <paragraph><content styleCode="bold underline">In case of an allergic emergency, use the real AUVI-Q and not the gray Trainer. Always carry your real Auvi-Q with you in case of an allergic emergency.</content></paragraph> <paragraph><content styleCode="bold">Important Information about the TRAINER for AUVI-Q: </content></paragraph><paragraph>Inside your TRAINER for AUVI-Q are: </paragraph><list listType="unordered" styleCode="Disc"><item>batteries </item><item>a speaker that will make a beeping sound and that produces electronic voice instructions</item><item>red and green blinking lights </item></list><paragraph>The TRAINER for AUVI-Q batteries are made to last long enough for you to practice 1 time each day for 2 years. If your TRAINER for AUVI-Q does not work properly call your healthcare provider for a new Trainer.</paragraph></td></tr></tbody></table>

tions</item><item>red and green blinking lights </item></list><paragraph>The TRAINER for AUVI-Q batteries are made to last long enough for you to practice 1 time each day for 2 years. If your TRAINER for AUVI-Q does not work properly call your healthcare provider for a new Trainer.</paragraph></td></tr></tbody></table> <table width="100%" cellpadding="5" styleCode="Noautorules"><col width="50%" align="left"/><col width="50%" align="left"/><tbody><tr valign="top"><td colspan="2"><content styleCode="bold">What is the TRAINER for AUVI-Q?</content><list listType="unordered" styleCode="disc"><item>The TRAINER for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection.</item><item>Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency.</item></list></td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Your TRAINER for AUVI-Q Figure A</content></td></tr><tr valign="top"><td align="center"><content styleCode="bold">TRAINER for AUVI-Q</content> <renderMultiMedia referencedObject="MM168"/> <content styleCode="bold">Top view</content><renderMultiMedia referencedObject="MM169"/></td><td align="center"><content styleCode="bold">AUVI-Q</content> <renderMultiMedia referencedObject="MM170"/> AUVI-Q 0.3 mg is <content styleCode="bold">orange</content> <renderMultiMedia referencedObject="MM171"/> AUVI-Q 0.15 mg is <content styleCode="bold">blue</content> <renderMultiMedia referencedObject="MM172"/> AUVI-Q 0.1 mg is <content styleCode="bold">white and lavender</content></td></tr><tr valign="top"><td><content styleCode="bold">TRAINER for AUVI-Q:</content><list listType="unordered" styleCode="disc"><item>is inside a <content styleCode="bold">gray outer case</content></item><item>does not have a needle or medicine inside</item><item>can be reused (the red safety guard can be placed back on the base of the Trainer after use)</item><item>has no expiration date</item><item>has embossed &#x201C;TRAINER&#x201D; on top of the device</item></list></td><td><content styleCode="bold">AUVI-Q: </content><list listType="unordered" styleCode="disc"><item>is inside <content styleCode="bold">an orange (0.3 mg)</content> or <content styleCode="bold">blue (0.15 mg)</content> or <content styleCode="bold">white and lavender (0.1 mg) outer case</content></item><item>contains a needle and epinephrine medicine</item><item><content styleCode="bold">cannot be reused</content> (AUVI-Q must be used or properly disposed once the red safety guard is removed)</item><item>has a medicine expiration date listed on the device</item></list></td></tr><tr valign="top"><td colspan="2">In case of an allergic emergency, use the real AUVI-Q and <content styleCode="bold">not</content> the gray Trainer.</td></tr><tr valign="top"><td colspan="2"> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Who should practice using the TRAINER for AUVI-Q?</content> Anyone who may need to help you with AUVI-Q in case of an allergic emergency: <list listType="unordered" styleCode="disc"><item>You</item><item>Caregivers</item><item>Family</item><item>Friends</item><item>Co-workers</item><item>Teachers</item><item>Child Care or Day Care Workers </item></list> Have them practice using the Trainer and review the Patient Information Leaflet included in the packaging with each prescription of AUVI-Q.

"disc"><item>You</item><item>Caregivers</item><item>Family</item><item>Friends</item><item>Co-workers</item><item>Teachers</item><item>Child Care or Day Care Workers </item></list> Have them practice using the Trainer and review the Patient Information Leaflet included in the packaging with each prescription of AUVI-Q. For more information and video instructions on the use of AUVI -Q, go to <linkHtml href="https://www.auvi-q.com">www.AUVI-Q.com</linkHtml> or call 1-877-302-8847.</td></tr><tr valign="top"><td colspan="2"> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Practicing with the TRAINER for AUVI-Q</content> Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency. <list listType="unordered" styleCode="disc"><item>You should practice daily for the first week after you receive your TRAINER for AUVI-Q to help you feel comfortable using AUVI-Q quickly and safely. Even when you are comfortable using the Trainer, continue to practice using it often.</item></list></td></tr><tr valign="top"><td colspan="2" align="left"><content styleCode="bold">How to Use the Trainer</content> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">How the TRAINER for AUVI-Q works</content> Although the Trainer does not have a needle and contains no medicine, it works the same way as the real AUVI-Q. As with the real AUVI-Q, the TRAINER for AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for the TRAINER for AUVI-Q for any reason, you can still use the TRAINER for AUVI-Q as instructed in this leaflet to practice. The TRAINER for AUVI-Q has the same blinking red and green lights as the real AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. </td></tr></tbody></table>

al AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. </td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="50%"/><col width="50%"/><tbody><tr valign="top"><td styleCode="Toprule Botrule Lrule Rrule" align="center" colspan="2"><content styleCode="bold">Follow These Steps</content></td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule" colspan="2" align="left"><content styleCode="bold">1.Pull the TRAINER for AUVI-Q from the outer case.</content> See <linkHtml href="#figureb1">Figure B</linkHtml><paragraph><content styleCode="bold">2. Pull Red safety guard down and off of the Trainer. </content>See <linkHtml href="#figurec1">Figure C</linkHtml>.</paragraph></td></tr><tr valign="top"><td styleCode="Lrule" align="center"><content ID="figureb1" styleCode="bold">Figure B <renderMultiMedia referencedObject="MM173"/></content></td><td styleCode="Rrule" align="center"><content ID="figurec1" styleCode="bold">Figure C <renderMultiMedia referencedObject="MM174"/></content></td></tr><tr valign="top"><td styleCode="Botrule Lrule Rrule" colspan="2" align="left">Note: The red safety guard is made to fit tight similar to the safety guard on the real AUVI-Q. <content styleCode="bold">Pull firmly to remove.</content></td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule" colspan="2" align="left"><content styleCode="bold">3. Place black end against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds.</content> See <linkHtml href="#figured1">Figure D</linkHtml>. <content styleCode="bold">As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. </content>(See <linkHtml href="#figuree1">Figure E</linkHtml>). </td></tr><tr><td styleCode="Lrule" align="center"><content ID="figured1" styleCode="bold">Figure D <renderMultiMedia referencedObject="MM175"/></content></td><td styleCode="Rrule" align="center"><content ID="figuree1" styleCode="bold">Figure E <renderMultiMedia referencedObject="MM176"/></content></td></tr><tr><td styleCode="Botrule Lrule Rrule" colspan="2" align="left">Note: In an actual emergency, after the injection you would seek medical care if needed. <content styleCode="bold">Only</content> practice using the middle of your outer thigh. The outer thigh is where you would inject with the real AUVI-Q. Note: The TRAINER for AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is the same sound that is made with the real AUVI-Q. This is normal, and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound.</td></tr><tr valign="top"><td styleCode="Toprule Lrule Rrule" colspan="2" align="left"><content styleCode="bold">4. After practicing, reset the TRAINER for AUVI-Q:</content> <content styleCode="bold"> a. Replace the Red safety guard.</content> Do not hold the black base while inserting the Red safety guard. The Black base will drop down into its original location during Red safety guard insertion. See <linkHtml href="#figuref1">Figure F</linkHtml>. <content styleCode="bold"> b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system. </content>See <linkHtml href="#figureg1">Figure G</linkHtml>.

down into its original location during Red safety guard insertion. See <linkHtml href="#figuref1">Figure F</linkHtml>. <content styleCode="bold"> b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system. </content>See <linkHtml href="#figureg1">Figure G</linkHtml>. </td></tr><tr><td styleCode="Lrule" align="center"><content ID="figuref1" styleCode="bold">Figure F <renderMultiMedia referencedObject="MM177"/></content></td><td styleCode="Rrule" align="center"><content ID="figureg1" styleCode="bold">Figure G <renderMultiMedia referencedObject="MM178"/></content></td></tr><tr><td styleCode="Botrule Lrule Rrule" colspan="2" align="left">Note: Leave the TRAINER for AUVI-Q in its outer case for at least 5 seconds between each time you practice to allow the electronic voice system to reset.</td></tr></tbody></table>

1 INDICATIONS AND USAGE AUVI-Q® is indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. AUVI-Q is intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions. Anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema. AUVI-Q is intended for immediate self-administration as emergency supportive therapy only and is not a substitute for immediate medical care. AUVI-Q is a non-selective alpha and beta-adrenergic receptor agonist indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis. ( 1 )

2 DOSAGE AND ADMINISTRATION Selection of the appropriate dosage strength (AUVI-Q 0.3 mg, AUVI-Q 0.15 mg or AUVI-Q 0.1 mg) is determined according to patient body weight. Patients greater than or equal to 30 kg (approximately 66 pounds or more): AUVI-Q 0.3 mg Patients 15 to 30 kg (33 to 66 pounds): AUVI-Q 0.15 mg Patients 7.5 to 15 kg (16.5 to 33 pounds): AUVI-Q 0.1 mg Inject AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Instruct caregivers of young children and infants who are prescribed AUVI-Q and who may be uncooperative and kick or move during an injection to hold the child’s leg firmly in place and limit movement prior to and during an injection [see Warnings and Precautions ( 5.2 )] . Each AUVI-Q contains a single dose of epinephrine for single-dose injection. Since the doses of epinephrine delivered from AUVI-Q are fixed, consider using other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary. The prescriber should carefully assess each patient to determine the most appropriate dose of epinephrine, recognizing the life-threatening nature of the reactions for which this drug is indicated. With severe persistent anaphylaxis, repeat injections with an additional AUVI-Q may be necessary. More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Warnings and Precautions ( 5.1 )] . The epinephrine solution in the viewing window of AUVI-Q should be inspected visually for particulate matter and discoloration. Epinephrine is light sensitive and should be stored in the outer case provided to protect it from light [see How Supplied/ Storage and Handling ( 16 )] . Patients greater than or equal to 30 kg (66 lbs): AUVI-Q 0.3 mg ( 2 ) Patients 15 to 30 kg (33 to 66 lbs): AUVI-Q 0.15 mg ( 2 ) Patients 7.5 to 15 kg (16.5 to 33 lbs): AUVI-Q 0.1 mg ( 2 ) Inject AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Each device is a single-dose injection. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Injection: 0.3 mg/0.3 mL epinephrine injection, USP, pre-filled autoinjector 0.15 mg/0.15 mL epinephrine injection, USP, pre-filled autoinjector 0.1 mg/0.1 mL epinephrine injection, USP, pre-filled autoinjector Injection: 0.3 mg: 0.3 mg/0.3 mL epinephrine injection, USP, pre-filled autoinjector ( 3 ) 0.15 mg: 0.15 mg/0.15 mL epinephrine injection, USP, pre-filled autoinjector ( 3 ) 0.1 mg: 0.1 mg/0.1 mL epinephrine injection, USP, pre-filled autoinjector ( 3 )

5 WARNINGS AND PRECAUTIONS In conjunction with use, seek immediate medical or hospital care. ( 5.1 ) Do not inject intravenously, into buttock, or into digits, hands, or feet. ( 5.2 ) To minimize the risk of injection-related injury, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection when administering to young children or infants. ( 5.2 ) 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 at the epinephrine injection site. ( 5.3 ) The presence of a sulfite in this product should not deter use. ( 5.4 ) Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. ( 5.5 ) 5.1 Emergency Treatment AUVI-Q is not intended as a substitute for immediate medical care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Indications and Usage ( 1 ), Dosage and Administration ( 2 ) and Patient Counseling Information ( 17 )] . 5.2 Injection-Related Complications AUVI-Q should ONLY be injected into the anterolateral aspect of the thigh [see Dosage and Administration ( 2 ) and Patient Counseling Information ( 17 )] . Do not inject intravenously. Large doses or accidental intravenous injection of 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. Advise the patient to go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with 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. 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. Advise the patient to go immediately to the nearest emergency room and to 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 AUVI-Q to young children or infants, instruct caregivers to hold the child’s leg firmly in place and limit movement prior to and during injection. 5.3 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 the presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores.

njection 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 the presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the potential risk of a rare, but serious Clostridium infection, do not inject AUVI-Q into the buttock [see Warnings and Precautions ( 5.2 )] . 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. 5.4 Allergic Reactions Associated with Sulfite Epinephrine is the preferred treatment for serious allergic reactions or other emergency situations even though this product 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 presence of a sulfite in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. 5.5 Disease Interactions 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, patients with these conditions, and/or any other person who might be in a position to administer AUVI-Q to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which epinephrine should be used. Patients with Heart Disease Epinephrine should be administered 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 Drug Interactions ( 7 ) and Adverse Reactions ( 6 )] . Other Patients and Diseases Epinephrine should be administered with caution to patients with hyperthyroidism, diabetes, elderly individuals, and pregnant women. Patients with Parkinson’s disease may notice a temporary worsening of symptoms.

6 ADVERSE REACTIONS Due to 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. Common adverse reactions to systemically administered epinephrine include anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/or respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism [see Warnings and Precautions ( 5.5 )] . Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or those receiving certain drugs [see Warnings and Precautions ( 5.5 ) and Drug Interactions ( 7 )] . Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions ( 5.5 )] . Angina may occur in patients with coronary artery disease [see Warnings and Precautions ( 5.5 )] . Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions ( 5.2 )] . Adverse events experienced as a result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury. Injection of epinephrine into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions ( 5.2 )] . 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 in the thigh [see Warnings and Precautions ( 5.2 )] . Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact kaleo, Inc. at 1-877-302-8847 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

7 DRUG INTERACTIONS Cardiac glycosides or diuretics: observe for development of cardiac arrhythmias. ( 7 ) Tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines: potentiate effects of epinephrine. ( 7 ) Beta-adrenergic blocking drugs: antagonize cardiostimulating and bronchodilating effects of epinephrine. ( 7 ) Alpha-adrenergic blocking drugs: antagonize vasoconstricting and hypertensive effects of epinephrine. ( 7 ) Ergot alkaloids: may reverse the pressor effects of epinephrine. ( 7 ) 7.1 Drugs Increasing Risk of Cardiac Arrhythmias Patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions ( 5.5 )] . 7.2 Drugs Potentiating Effects of Epinephrine The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine. 7.3 Drugs Antagonizing Effects of Epinephrine The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol. The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine. Ergot alkaloids may also reverse the pressor effects of epinephrine.

8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 5.5 , 8.5 ) 8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days). 8.2 Lactation Risk Summary There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients. 8.4 Pediatric Use AUVI-Q may be administered to pediatric patients at a dosage appropriate to body weight [see Dosage and Administration ( 2 )] .

uction. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients. 8.4 Pediatric Use AUVI-Q may be administered to pediatric patients at a dosage appropriate to body weight [see Dosage and Administration ( 2 )] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from AUVI-Q are fixed, consider using other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary. 8.5 Geriatric Use Clinical studies of AUVI-Q did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Epinephrine should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [see Warnings and Precautions ( 5.5 ), Overdosage ( 10 )] .

8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days).

8.4 Pediatric Use AUVI-Q may be administered to pediatric patients at a dosage appropriate to body weight [see Dosage and Administration ( 2 )] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from AUVI-Q are fixed, consider using other forms of injectable epinephrine if doses lower than 0.1 mg are deemed necessary.

8.5 Geriatric Use Clinical studies of AUVI-Q did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Epinephrine should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [see Warnings and Precautions ( 5.5 ), Overdosage ( 10 )] .

10 OVERDOSAGE Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Treatment consists of rapidly acting vasodilators or alpha-adrenergic blocking drugs and/or respiratory support. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia, and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol. Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis, and kidney failure. Suitable corrective measures must be taken in such situations.

11 DESCRIPTION AUVI-Q (epinephrine injection, USP) 0.3 mg, 0.15 mg and 0.1 mg is an autoinjector and a combination product containing drug and device components. AUVI-Q includes audible (electronic voice instructions, beeps) and visible (LED lights) cues for use. The needle automatically retracts after the injection is complete. Each AUVI-Q 0.3 mg delivers a single dose of 0.3 mg epinephrine from epinephrine injection, USP (0.3 mL) in a sterile solution. Each AUVI-Q 0.15 mg delivers a single dose of 0.15 mg epinephrine from epinephrine injection, USP (0.15 mL) in a sterile solution. Each AUVI-Q 0.1 mg delivers a single dose of 0.1 mg epinephrine from epinephrine injection, USP (0.1 mL) in a sterile solution . AUVI-Q 0.3 mg, AUVI-Q 0.15 mg and AUVI-Q 0.1 mg each contain 0.76 mL epinephrine solution. 0.3 mL, 0.15 mL and 0.1 mL epinephrine solution is dispensed for AUVI-Q 0.3 mg, AUVI-Q 0.15 mg and AUVI-Q 0.1 mg, respectively, when activated. The remaining solution is not available for future use and should be discarded. Each 0.3 mL in AUVI-Q 0.3 mg contains 0.3 mg epinephrine, 2.3 mg sodium chloride, 0.5 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2–5.0. Each 0.15 mL in AUVI-Q 0.15 mg contains 0.15 mg epinephrine, 1.2 mg sodium chloride, 0.2 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2–5.0. Each 0.1 mL in AUVI-Q 0.1 mg contains 0.1 mg epinephrine, 0.78 mg sodium chloride, 0.15 mg sodium bisulfite, hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2–5.0. Epinephrine is a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4-Dihydroxy-α-[(methylamino)methyl]benzyl alcohol with the following structure: Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. AUVI-Q is not made with natural rubber latex. AUVI-Q instructional and safety systems should be thoroughly reviewed with patients and caregivers prior to use [see Patient Counseling Information ( 17 )] . Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha and beta-adrenergic receptors. 12.2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

12.2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under the Indications and Usage ( 1 ) . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under the Indications and Usage ( 1 ) . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied AUVI-Q (epinephrine injection) is available as an autoinjector as described in Table 1 . Table 1 AUVI-Q Autoinjector Package Configurations and Strengths Package Configuration Strength National Drug Code (NDC) 2 autoinjectors 0.3 mg NDC 60842-023-02 2 autoinjectors 0.15 mg NDC 60842-022-02 2 autoinjectors 0.1 mg NDC 60842-021-02 Storage and Handling Epinephrine is light sensitive and should be stored in the outer case provided to protect it from light. Store at 20℃ to 25℃ (68℉ to 77℉); excursions permitted to 15℃ to 30℃℉ (59℉ to 86℉) [See USP Controlled Room Temperature]. Do not freeze. Before using, check to make sure the solution in the autoinjector is clear and colorless. Replace the autoinjector if the solution is discolored, cloudy, or contains particles.

<table width="750" styleCode="Noautorules"><col width="34%" align="center"/><col width="32%" align="center"/><col width="34%" align="center"/><tbody valign="top"><tr><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Package Configuration</content></td><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Strength</content></td><td styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">National Drug Code (NDC)</content></td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.3 mg</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-023-02</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.15 mg</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-022-02</td></tr><tr><td styleCode="Toprule Botrule Lrule Rrule">2 autoinjectors</td><td styleCode="Toprule Botrule Lrule Rrule">0.1 mg</td><td styleCode="Toprule Botrule Lrule Rrule">NDC 60842-021-02</td></tr></tbody></table>

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). A healthcare provider should review the patient instructions and operation of AUVI-Q, in detail, with the patient or caregiver. Epinephrine is essential for the treatment of anaphylaxis. Patients who are at risk of or with a history of severe allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, as well as idiopathic and exercise-induced anaphylaxis, should be carefully instructed about the circumstances under which epinephrine should be used. Administration and Training Instruct patients and/or caregivers in the appropriate use of AUVI-Q. AUVI-Q should be injected into the middle of the outer thigh (through clothing, if necessary). Each device is a single-dose injection. Advise patients to seek immediate medical care in conjunction with administration of AUVI-Q. Young children or infants may be uncooperative and kick or move during an injection. Instruct caregivers to hold the leg of young children or infants firmly in place and limit movement prior to and during injection [see Warnings and Precautions ( 5.2 )] . Complete patient information, including dosage, directions for proper administration and precautions can be found inside each AUVI-Q carton. Review AUVI-Q’s instructional and safety systems with patients and/or caregivers. These systems include the printed label on the surface of AUVI-Q showing instructions for use and a diagram depicting the injection process, an automatic needle retraction system, visual prompts, electronic beeps, and voice instructions for use. Instruct patients and/or caregivers that the needle will not be visible after the injection and they may not feel the injection when it occurs. Instruct patients that AUVI-Q includes a 2-second countdown after it is activated and then the voice instructions will indicate the injection is complete and to seek emergency medical attention. Instruct patients that AUVI-Q’s black base will lock up onto the device housing and the lights will blink red after the injection is complete. These post-use indicators help patients and/or caregivers know that AUVI-Q has been activated and an epinephrine injection administered. Instruct patients and/or caregivers to use and practice with the Trainer to familiarize themselves with the use of AUVI-Q in an allergic emergency. The Trainer may be used multiple times. Adverse Reactions Epinephrine may produce symptoms and signs that include an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbency. Patients with hypertension or hyperthyroidism may develop more severe or persistent effects, and patients with coronary artery disease could experience angina. Patients with diabetes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms [see Warnings and Precautions ( 5.5 )] . Accidental Injection Patients should be advised to seek immediate medical care in the case of accidental injection.

tes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms [see Warnings and Precautions ( 5.5 )] . Accidental Injection Patients should be advised to seek immediate medical care in the case of accidental injection. Since epinephrine is a strong vasoconstrictor when injected into the digits, hands, or feet, treatment should be directed at vasodilatation if there is such an accidental injection to these areas [see Warnings and Precautions ( 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 [see Warnings and Precautions ( 5.3 )] . Storage and Handling Patients should be instructed to inspect the epinephrine solution visually through the viewing window periodically. AUVI-Q should be replaced if the epinephrine solution appears discolored (pinkish color or darker than slightly yellow), cloudy, or contains particles. Epinephrine is light sensitive and should be stored in the outer case provided to protect it from light. Instruct patients that AUVI-Q must be used or properly disposed once the red safety guard is removed [see How Supplied/ Storage and Handling ( 16 )] . Complete patient information, including dosage, directions for proper administration and precautions can be found inside each AUVI-Q carton. Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO ® and AUVI-Q ® are registered trademarks of kaleo, Inc. © 2024 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate

PATIENT INFORMATION AUVI-Q® [Aw-Vee-Kyoo] (epinephrine injection) Auto-Injector For allergic emergencies (anaphylaxis) Read this Patient Information Leaflet before you have to use AUVI-Q and each time you get a refill. There may be new information. You should know how to use AUVI-Q before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about AUVI-Q? Always carry AUVI-Q with you because you may not know when a life-threatening allergic reaction (anaphylactic reaction) may happen. Talk to your doctor if you need additional units to keep at work, school, etc. An anaphylactic reaction is a life-threatening allergic reaction that can happen within minutes and can be caused by stinging and biting insects (bees, wasps, hornets, and mosquitoes), allergy shots, foods, medicines, exercise, or other unknown causes. Follow your healthcare provider’s instructions on when to use AUVI-Q if you have the symptoms of an anaphylactic reaction, which may include the symptoms listed below: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements dizziness or fainting Tell your family members and others where you keep AUVI-Q and how to use it before you need it. You may be unable to speak in an allergic emergency. Get medical attention immediately after using AUVI-Q. If you have a serious allergic reaction, you may need more medicine. What is AUVI-Q? AUVI-Q is a prescription medicine used to treat life-threatening allergic reactions including anaphylaxis in people who are at risk for or have a history of serious allergic reactions. AUVI-Q is for immediate self (or caregiver) administration and does not take the place of emergency medical care. You should get emergency medical help right away after using AUVI-Q. It is not known if AUVI-Q is safe and effective in children who weigh less than 16.5 pounds (7.5 kg). What should I tell my healthcare provider before using AUVI-Q? Before you use AUVI-Q, tell your healthcare provider if you: have heart problems or high blood pressure have diabetes have thyroid problems have history of depression have Parkinson’s disease have any other medical conditions are pregnant or plan to become pregnant. It is not known if AUVI-Q will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if AUVI-Q passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. AUVI-Q and other medicines may affect each other, causing side effects. AUVI-Q may affect the way other medicines work, and other medicines may affect how AUVI-Q works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use AUVI-Q? Each AUVI-Q contains only 1 dose of medicine. AUVI-Q should only be injected into the muscle of your outer thigh. It can be injected through your clothing, if needed.

s. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use AUVI-Q? Each AUVI-Q contains only 1 dose of medicine. AUVI-Q should only be injected into the muscle of your outer thigh. It can be injected through your clothing, if needed. Read the Instructions for Use at the end of this Patient Information Leaflet for information about the right way to use AUVI-Q. Use AUVI-Q exactly as your healthcare provider tells you to use it. You may request a Trainer for AUVI-Q. Additional training resources are available at www.auvi-q.com . Practice with the Trainer for AUVI-Q before an allergic emergency happens to familiarize yourself with the use of AUVI-Q in an allergic emergency. The Trainer for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection. What are the possible side effects of AUVI-Q? AUVI-Q may cause serious side effects. AUVI-Q should only be injected into your outer thigh. Do not inject AUVI-Q into your: veins buttocks fingers, toes, hands or feet If you accidentally inject AUVI-Q into any other part of your body, go to the nearest hospital emergency room right away. Tell the healthcare provider where on your body you received the accidental injection. Rarely, patients who use AUVI-Q may develop infections at the injection site within a few days of an injection. Some of these infections can be serious. Call your healthcare provider right away if you have any of the following at an injection site: redness that does not go away swelling tenderness the area feels warm to the touch If you inject a young child or infant with AUVI-Q, hold their leg firmly in place before and during the injection to prevent injuries. Ask your healthcare provider to show you how to properly hold the leg of a young child or infant during an injection. If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have more or longer lasting side effects when you use AUVI-Q. Talk to your healthcare provider about all your medical conditions. Common side effects of AUVI-Q include: fast, irregular, or ‘pounding’ heart beat sweating shakiness headache paleness feelings of over excitement, nervousness, or anxiety weakness dizziness nausea and vomiting breathing problems Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of AUVI-Q. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store AUVI-Q? Store AUVI-Q at 68° to 77°F (20° to 25°C). Do NOT freeze. Do NOT expose to extreme heat or cold. For example, do NOT store in your vehicle’s glove box. Examine contents in the viewing window periodically. Solution should be clear. If the solution is discolored (pinkish color or darker than slightly yellow), cloudy or contains solid particles, replace the unit. Your AUVI-Q has an expiration date. Replace it before the expiration date. Keep AUVI-Q in the outer case it comes in to protect it from light. Keep AUVI-Q and all medicines out of the reach of children. General information about the safe and effective use of AUVI-Q: Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use AUVI-Q for a condition for which it was not prescribed. Do not give AUVI-Q to other people, even if they have an allergic reaction or the same symptoms that you have. It may harm them. This Patient Information Leaflet summarizes the most important information about AUVI-Q. If you would like more information, talk to your healthcare provider.

for which it was not prescribed. Do not give AUVI-Q to other people, even if they have an allergic reaction or the same symptoms that you have. It may harm them. This Patient Information Leaflet summarizes the most important information about AUVI-Q. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about AUVI-Q that is written for health professionals. For more information and video instructions on the use of AUVI-Q, go to www.auvi-q.com or call 1-877-302-8847. What are the ingredients in AUVI-Q? Active ingredient: epinephrine. Inactive Ingredients: sodium chloride, sodium bisulfite, hydrochloric acid, and water. AUVI-Q does not contain latex. Instructions for Use Read these Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Automated Voice Instructions AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency. How to use your AUVI-Q Figure A. 1. Pull AUVI-Q up from the outer case. See Figure B . Do not go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. Figure B. 2. Pull Red safety guard down and off of AUVI-Q. See Figure C . To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. Note: The red safety guard is made to fit tight. Pull firmly to remove. Figure C. 3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . Only inject into the middle of the outer thigh. Do not inject into any other part of the body. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place while administering an injection See Figure E . Figure D. (For AUVI-Q 0.3 mg and AUVI-Q 0.15 mg) Figure E. (For AUVI-Q 0.1 mg) Note: AUVI-Q makes a distinct sound (click and hiss) when you push it against your outer thigh. This is normal and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. The needle automatically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek emergency medical attention, AUVI-Q will beep, and the lights will blink red. 4. Get emergency medical help right away. Replace the outer case and talk to your healthcare provider about the right way to throw away your AUVI-Q. Ask your healthcare provider for an AUVI-Q prescription refill. After the use of AUVI-Q: The black base will lock into place. The voice instruction system will say “seek emergency medical attention”, say “this AUVI-Q has been used…”, and the lights will blink red. Do not replace the red safety guard. The viewing window will no longer be clear. It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q.

s AUVI-Q has been used…”, and the lights will blink red. Do not replace the red safety guard. The viewing window will no longer be clear. It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q. AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed once the red safety guard is removed. Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed. If you will be administering AUVI-Q to a young child or infant, ask your healthcare provider to show you how to properly hold the leg in place while administering a dose. This Patient Information has been approved by the U.S. Food and Drug Administration. Rev. Feb 2024 Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2024 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate Figure A Figure B Figure C Figure D Figure E

Instructions for Use Read these Instructions for Use carefully before you need to use your AUVI-Q. Before you use AUVI-Q, make sure your healthcare provider shows you the right way to use it. If you have any questions, ask your healthcare provider. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place and limit movement prior to and while administering an injection. Automated Voice Instructions AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for any reason, use AUVI-Q as instructed in these Instructions for Use. It will still work during an allergic reaction emergency. How to use your AUVI-Q Figure A. 1. Pull AUVI-Q up from the outer case. See Figure B . Do not go to step 2 until you are ready to use AUVI-Q. If you are not ready to use AUVI-Q, put it back in the outer case. Figure B. 2. Pull Red safety guard down and off of AUVI-Q. See Figure C . To reduce the chance of an accidental injection, do not touch the black base of the auto-injector, which is where the needle comes out. If an accidental injection happens, get medical help right away. Note: The red safety guard is made to fit tight. Pull firmly to remove. Figure C. 3. Place black end of AUVI-Q against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . Only inject into the middle of the outer thigh. Do not inject into any other part of the body. If you are administering AUVI-Q to a young child or infant, hold the leg firmly in place while administering an injection See Figure E . Figure D. (For AUVI-Q 0.3 mg and AUVI-Q 0.15 mg) Figure E. (For AUVI-Q 0.1 mg) Note: AUVI-Q makes a distinct sound (click and hiss) when you push it against your outer thigh. This is normal and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. The needle automatically retracts after the injection is complete, so the needle will not be visible after the injection. AUVI-Q includes a 2-second countdown after it is activated, then the voice instruction will indicate the injection is complete, and to seek emergency medical attention, AUVI-Q will beep, and the lights will blink red. 4. Get emergency medical help right away. Replace the outer case and talk to your healthcare provider about the right way to throw away your AUVI-Q. Ask your healthcare provider for an AUVI-Q prescription refill. After the use of AUVI-Q: The black base will lock into place. The voice instruction system will say “seek emergency medical attention”, say “this AUVI-Q has been used…”, and the lights will blink red. Do not replace the red safety guard. The viewing window will no longer be clear. It is normal for some medicine to remain in your AUVI-Q after you have received your dose of medicine. Talk to your healthcare provider about the right way to throw away your AUVI-Q. AUVI-Q is a single-dose auto-injector and cannot be reused. AUVI-Q must be used or properly disposed once the red safety guard is removed. Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed. If you will be administering AUVI-Q to a young child or infant, ask your healthcare provider to show you how to properly hold the leg in place while administering a dose.

Until you throw away your used AUVI-Q, the electronic voice instruction system will remind you that it has been used when the outer case is removed. If you will be administering AUVI-Q to a young child or infant, ask your healthcare provider to show you how to properly hold the leg in place while administering a dose. This Patient Information has been approved by the U.S. Food and Drug Administration. Rev. Feb 2024 Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2024 kaleo, Inc. *For California Only: This product uses batteries containing Perchlorate Material – special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate Figure A Figure B Figure C Figure D Figure E

and green lights as the real AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. Follow These Steps 1.Pull the TRAINER for AUVI-Q from the outer case. See Figure B 2. Pull Red safety guard down and off of the Trainer. See Figure C . Figure B Figure C Note: The red safety guard is made to fit tight similar to the safety guard on the real AUVI-Q. Pull firmly to remove. 3. Place black end against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds. See Figure D . As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. (See Figure E ). Figure D Figure E Note: In an actual emergency, after the injection you would need to seek medical help right away. Only practice using the middle of your outer thigh. The outer thigh is where you would inject with the real AUVI-Q. Note: The TRAINER for AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is the same sound that is made with the real AUVI-Q. This is normal, and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. 4. After practicing, reset the TRAINER for AUVI-Q: a. Replace the Red safety guard. Do not hold the black base while inserting the Red safety guard. The Black base will drop down into its original location during Red safety guard insertion. See Figure F . b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system. See Figure G . Figure F Figure G Note: Leave the TRAINER for AUVI-Q in its outer case for at least 5 seconds between each time you practice to allow the electronic voice system to reset. Storage: Store the TRAINER for AUVI-Q at room temperature; the TRAINER for AUVI-Q should not be used at temperatures less than 50°F (10°C) or greater than 104°F (40°C). Store the TRAINER for AUVI-Q in its outer case. Keep the TRAINER for AUVI-Q away from dirt, chemicals, and water. Disposal: The TRAINER for AUVI-Q contains electronics and lithium coin cell batteries, and should be disposed of in the correct manner. Follow your State and local environmental regulations for disposal. For California Only: This product uses batteries containing Perchlorate Material - special handling may apply. See www.dtsc.ca.gov/hazardouswaste/perchlorate Manufactured for: kaleo, Inc. Richmond, VA 23219 USA This product may be covered by one or more U.S. patents or pending patent applications; see www.kaleo.com for details. KALÉO® and AUVI-Q® are registered trademarks of kaleo, Inc. © 2024 kaleo, Inc. Rev. Feb 2024 Figure A1 Figure A2 Figure A3 Figure A4 Figure A5 Figure B Figure C Figure D Figure E Figure F Figure G

<table width="100%" cellpadding="5" styleCode="Noautorules"><col width="50%" align="left"/><col width="50%" align="left"/><tbody><tr valign="top"><td colspan="2"><content styleCode="bold">What is the TRAINER for AUVI-Q?</content><list listType="unordered" styleCode="Disc"><item>The TRAINER for AUVI-Q does not contain a needle or medicine and can be reused to practice your injection.</item><item>Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency.</item></list></td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Your TRAINER for AUVI-Q Figure A </content></td></tr><tr valign="top"><td align="center"><content styleCode="bold">TRAINER for AUVI-Q</content> <renderMultiMedia referencedObject="MM168"/> <content styleCode="bold">Top view</content><renderMultiMedia referencedObject="MM169"/></td><td align="center"><content styleCode="bold">AUVI-Q</content> <renderMultiMedia referencedObject="MM170"/> AUVI-Q 0.3 mg is <content styleCode="bold">orange</content> <renderMultiMedia referencedObject="MM171"/> AUVI-Q 0.15 mg is <content styleCode="bold">blue</content> <renderMultiMedia referencedObject="MM172"/> AUVI-Q 0.1 mg is <content styleCode="bold">white and lavender</content></td></tr><tr valign="top"><td><content styleCode="bold">TRAINER for AUVI-Q:</content><list listType="unordered" styleCode="Disc"><item>is inside a <content styleCode="bold">gray outer case</content></item><item>does not have a needle or medicine inside</item><item>can be reused (the red safety guard can be placed back on the base of the Trainer after use)</item><item>has no expiration date</item><item>has embossed &#x201C;TRAINER&#x201D; on top of the device</item></list></td><td><content styleCode="bold">AUVI-Q:</content><list listType="unordered" styleCode="Disc"><item>is inside <content styleCode="bold">an orange (0.3 mg)</content>or <content styleCode="bold">blue (0.15 mg)</content>or <content styleCode="bold">white and lavender (0.1 mg) outer case</content></item><item>contains a needle and epinephrine medicine</item><item><content styleCode="bold">cannot be reused</content>(AUVI-Q must be used or properly disposed once the red safety guard is removed) </item><item>has a medicine expiration date listed on the device</item></list></td></tr><tr valign="top"><td colspan="2">In case of an allergic emergency, use the real AUVI-Q and <content styleCode="bold">not</content>the gray Trainer. </td></tr><tr valign="top"><td colspan="2"> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Who should practice using the TRAINER for AUVI-Q?</content> Anyone who may need to help you with AUVI-Q in case of an allergic emergency: <list listType="unordered" styleCode="Disc"><item>You</item><item>Caregivers</item><item>Family</item><item>Friends</item><item>Co-workers</item><item>Teachers</item><item>Child Care or Day Care Workers</item></list>Have them practice using the Trainer and review the Patient Information Leaflet included in the packaging with each prescription of AUVI-Q. For more information and video instructions on the use of AUVI -Q, go to <linkHtml href="https://www.auvi-q.com">www.AUVI-Q.com</linkHtml>or call 1-877-302-8847.

rkers</item></list>Have them practice using the Trainer and review the Patient Information Leaflet included in the packaging with each prescription of AUVI-Q. For more information and video instructions on the use of AUVI -Q, go to <linkHtml href="https://www.auvi-q.com">www.AUVI-Q.com</linkHtml>or call 1-877-302-8847. </td></tr><tr valign="top"><td colspan="2"> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">Practicing with the TRAINER for AUVI-Q</content> Practice with the TRAINER for AUVI-Q before an allergic emergency happens to make sure you are able to safely use the real AUVI-Q in an emergency. <list listType="unordered" styleCode="Disc"><item>You should practice daily for the first week after you receive your TRAINER for AUVI-Q to help you feel comfortable using AUVI-Q quickly and safely. Even when you are comfortable using the Trainer, continue to practice using it often.</item></list></td></tr><tr valign="top"><td colspan="2" align="left"><content styleCode="bold">How to Use the Trainer</content> </td></tr><tr valign="top"><td colspan="2"><content styleCode="bold">How the TRAINER for AUVI-Q works</content> Although the Trainer does not have a needle and contains no medicine, it works the same way as the real AUVI-Q. As with the real AUVI-Q, the TRAINER for AUVI-Q contains an electronic voice instruction system to help guide you through each step of your injection. If the voice instructions do not work for the TRAINER for AUVI-Q for any reason, you can still use the TRAINER for AUVI-Q as instructed in this leaflet to practice. The TRAINER for AUVI-Q has the same blinking red and green lights as the real AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. </td></tr></tbody></table>

al AUVI-Q. As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q. Ask your healthcare provider to show you how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. </td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="50%"/><col width="50%"/><tbody><tr valign="top"><td align="center" colspan="2" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Follow These Steps</content></td></tr><tr valign="top"><td colspan="2" align="left" styleCode="Toprule Lrule Rrule"><content styleCode="bold">1.Pull the TRAINER for AUVI-Q from the outer case.</content>See <linkHtml href="#figureb1">Figure B</linkHtml><paragraph><content styleCode="bold">2. Pull Red safety guard down and off of the Trainer.</content>See <linkHtml href="#figurec1">Figure C</linkHtml>. </paragraph></td></tr><tr valign="top"><td align="center" styleCode="Lrule"><content styleCode="bold">Figure B <renderMultiMedia referencedObject="MM173"/></content></td><td align="center" styleCode="Rrule"><content styleCode="bold">Figure C <renderMultiMedia referencedObject="MM174"/></content></td></tr><tr valign="top"><td colspan="2" align="left" styleCode="Botrule Lrule Rrule">Note: The red safety guard is made to fit tight similar to the safety guard on the real AUVI-Q. <content styleCode="bold">Pull firmly to remove.</content></td></tr><tr valign="top"><td colspan="2" align="left" styleCode="Toprule Lrule Rrule"><content styleCode="bold">3. Place black end against the middle of the outer thigh (through clothing, if needed), then push firmly until you hear a click and hiss sound, and hold in place for 2 seconds.</content>See <linkHtml href="#figured1">Figure D</linkHtml>. <content styleCode="bold">As with the real AUVI-Q, if practicing with a young child or infant, hold the leg firmly in place while using the TRAINER for AUVI-Q.</content>(See <linkHtml href="#figuree1">Figure E</linkHtml>). </td></tr><tr><td align="center" styleCode="Lrule"><content styleCode="bold">Figure D <renderMultiMedia referencedObject="MM175"/></content></td><td align="center" styleCode="Rrule"><content styleCode="bold">Figure E <renderMultiMedia referencedObject="MM176"/></content></td></tr><tr><td colspan="2" align="left" styleCode="Botrule Lrule Rrule">Note: In an actual emergency, after the injection you would need to seek medical help right away. <content styleCode="bold">Only</content>practice using the middle of your outer thigh. The outer thigh is where you would inject with the real AUVI-Q. Note: The TRAINER for AUVI-Q makes a distinct sound (click and hiss) when you push it firmly against your outer thigh. This is the same sound that is made with the real AUVI-Q. This is normal, and indicates AUVI-Q is working correctly. Do not pull AUVI-Q away from your leg when you hear the click and hiss sound. </td></tr><tr valign="top"><td colspan="2" align="left" styleCode="Toprule Lrule Rrule"><content styleCode="bold">4. After practicing, reset the TRAINER for AUVI-Q:</content> <content styleCode="bold"> a. Replace the Red safety guard.</content>Do not hold the black base while inserting the Red safety guard. The Black base will drop down into its original location during Red safety guard insertion. See <linkHtml href="#figuref1">Figure F</linkHtml>. <content styleCode="bold"> b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system.</content>See <linkHtml href="#figureg1">Figure G</linkHtml>.

p down into its original location during Red safety guard insertion. See <linkHtml href="#figuref1">Figure F</linkHtml>. <content styleCode="bold"> b. Slide the TRAINER for AUVI-Q all the way back into the gray outer case to reset the electronic voice system.</content>See <linkHtml href="#figureg1">Figure G</linkHtml>. </td></tr><tr><td align="center" styleCode="Lrule"><content styleCode="bold">Figure F <renderMultiMedia referencedObject="MM177"/></content></td><td align="center" styleCode="Rrule"><content styleCode="bold">Figure G <renderMultiMedia referencedObject="MM178"/></content></td></tr><tr><td colspan="2" align="left" styleCode="Botrule Lrule Rrule">Note: Leave the TRAINER for AUVI-Q in its outer case for at least 5 seconds between each time you practice to allow the electronic voice system to reset.</td></tr></tbody></table>

1 INDICATIONS AND USAGE Epinephrine is a non-selective alpha and beta adrenergic agonist indicated: • To increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. ( 1.1 ) • For emergency treatment of allergic reactions (Type 1), including anaphylaxis. ( 1.2 ) • For induction and maintenance of mydriasis during intraocular surgery. ( 1.3 ) 1.1 Hypotension associated with Septic Shock Epinephrine Injection USP, 1 mg/mL is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. 1.2 Anaphylaxis Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue. 1.3 Induction and Maintenance of Mydriasis during Intraocular Surgery Induction and maintenance of mydriasis during intraocular surgery.

2 DOSAGE AND ADMINISTRATION • Hypotension associated with septic shock ( 2.2 ): o Dilute epinephrine in dextrose solution prior to infusion. o Infuse epinephrine into a large vein. o Titrate 0.05 mcg/kg/min to 2 mcg/kg/min to achieve desired blood pressure. o Wean gradually. • Anaphylaxis ( 2.3 ) : Administer intramuscularly or subcutaneously into anterolateral thigh every 5-10 minutes as needed. o Adults and children over 30 kg (66 lb): 0.3-0.5 mg (0.3-0.5 mL) o Children under 30 kg (66 lb): 0.01 mg/kg (0.01 mL/kg) • Intraocular surgery ( 2.4 ) : o Dilute 1 mL with 100 to 1000 mL of an ophthalmic irrigation fluid, for ophthalmic irrigation or intracameral injection. 2.1 General Considerations Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is colored or cloudy, or if it contains particulate matter. Discard any unused portion. 2.2 Hypotension associated with Septic Shock Dilute epinephrine in 5 percent dextrose solution or 5 percent dextrose and sodium chloride solution. These dextrose containing fluids provide protection against significant loss of potency by oxidation. Administration in saline solution alone is not recommended . Whole blood or plasma, if indicated to increase blood volume, should be administered separately. Add 1 mL (1 mg) of epinephrine from its vial to 1,000 mL of a 5 percent dextrose containing solution. Each mL of this dilution contains 1 mcg of epinephrine. Correct blood volume depletion as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, epinephrine can be administered before and concurrently with blood volume replacement. Whenever possible, give infusions of epinephrine into a large vein. Avoid using a catheter tie-in technique, because the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug. Occlusive vascular diseases (for example, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger's disease) are more likely to occur in the lower than in the upper extremity; therefore, avoid the veins of the leg in elderly patients or in those suffering from such disorders. There is potential for gangrene in a lower extremity when infusions of catecholamine are given in an ankle vein. To provide hemodynamic support in septic shock associated hypotension in adult patients, the suggested dosing infusion rate of intravenously administered epinephrine is 0.05 mcg/kg/min to 2 mcg/kg/min, and is titrated to achieve a desired mean arterial pressure (MAP). The dosage may be adjusted periodically, such as every 10 to 15 minutes, in increments of 0.05 mcg/kg/min to 0.2 mcg/kg/min, to achieve the desired blood pressure goal. Continuous epinephrine infusion is generally required over several hours or days until the patient's hemodynamic status improves. The duration of perfusion or total cumulative dose cannot be predicted. After hemodynamic stabilization, wean incrementally over time, such as by decreasing doses of epinephrine every 30 minutes over a 12- to 24-hour period. 2.3 Anaphylaxis Inject epinephrine intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary.

se cannot be predicted. After hemodynamic stabilization, wean incrementally over time, such as by decreasing doses of epinephrine every 30 minutes over a 12- to 24-hour period. 2.3 Anaphylaxis Inject epinephrine intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. When administering to a child, to minimize the risk of injection related injury, hold the leg firmly in place and limit movement prior to and during an injection. The injection may be repeated every 5 to 10 minutes as necessary. For intramuscular administration, use a needle long enough (at least 1/2 inch to 5/8 inch) to ensure the injection is administered into the muscle. Monitor the patient clinically for the severity of the allergic reaction and potential cardiac effects of the drug, with repeat doses titrated to effect. Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis. Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0.5 mL) of undiluted epinephrine administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects. Children less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of undiluted epinephrine administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects. 2.4 Induction and Maintenance of Mydriasis during Intraocular Surgery Epinephrine must be diluted prior to intraocular use. Dilute 1 mL of epinephrine 1 mg/mL (1:1000) in 100 to 1000 mL of an ophthalmic irrigation fluid to create an epinephrine concentration of 1:100,000 to 1:1,000,000 (10 mcg/mL to 1 mcg/mL). Use the irrigating solution as needed for the surgical procedure. After dilution in an ophthalmic irrigating fluid, epinephrine may also be injected intracamerally as a bolus dose of 0.1 mL at a dilution of 1:100,000 to 1:400,000 (10 mcg/mL to 2.5 mcg/mL).

3 DOSAGE FORMS AND STRENGTHS Injection solution: 1 mg/mL epinephrine as a sterile solution in a 1 mL single-dose glass vial, marked Epinephrine Injection USP, 1 mg/mL. Injection solution: 1 mg/mL single dose vial. ( 3 )

5 WARNINGS AND PRECAUTIONS • Monitor patient for acute severe hypertension. ( 5.1 ) • Avoid extravasation into tissues, which can cause local necrosis. ( 5.2 ) • Do not inject into buttocks, digits, hands, or feet. ( 5.3 ) • Potential for pulmonary edema, which may be fatal. ( 5.4 ) • May constrict renal blood vessels and decrease urine formation. ( 5.5 ) • May induce potentially serious cardiac arrhythmias or aggravate angina pectoris, particularly in patients with underlying heart disease. ( 5.6 ) • Presence of sulfite in this product should not deter use. ( 5.10 ) 5.1 Hypertension When Epinephrine Injection is administered intravenously, titrate the infusion while monitoring vital signs. Invasive arterial blood pressure monitoring and central venous pressure monitoring are recommended. Because of varying response to epinephrine, dangerously high blood pressure may occur [see Drug Interactions ( 7 )] . 5.2 Extravasation and Tissue Necrosis with Intravenous Infusion When Epinephrine Injection is administered intravenously, the infusion site should be checked frequently for free flow. Avoid extravasation of epinephrine into the tissues, to prevent local necrosis. 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. 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. 5.3 Incorrect Locations of Injection for Anaphylaxis When Epinephrine Injection is used for the treatment of anaphylaxis, the most appropriate location for administration is into the anterolateral aspect of the thigh (vastus lateralis muscle) 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. 5.4 Pulmonary Edema When Epinephrine Injection is administered intravenously, there is risk of pulmonary edema because of the peripheral constriction and cardiac stimulation produced.

ction into the digits, hands or feet may result in loss of blood flow to the affected area and has been associated with tissue necrosis. 5.4 Pulmonary Edema When Epinephrine Injection is administered intravenously, there is risk of pulmonary edema because of the peripheral constriction and cardiac stimulation produced. Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. 5.5 Renal Impairment Intravenously administered epinephrine initially may produce constriction of renal blood vessels and decrease urine formation. 5.6 Cardiac Arrhythmias and Ischemia Epinephrine may induce cardiac arrhythmias and angina pectoris in patients, especially patients suffering from coronary artery disease, organic heart disease, cerebrovascular disease, hypertension, or patients who are receiving drugs that sensitize the myocardium [see Adverse Reactions ( 6 ) and Drug Interactions ( 7 )]. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). 5.7 Injury with Undiluted Intraocular Solution Epinephrine must be diluted before intraocular use. Other epinephrine products that contain sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL). Warning is advised [see Dosage and Administration ( 2.4 )] . 5.8 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 ( 5.3 )]. 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. 5.9 Other Disease Interactions 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. Despite these concerns, the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. 5.10 Risk of 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 a sulfite(s) in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations.

6 ADVERSE REACTIONS Most common adverse reactions to systemically administered epinephrine are headache; anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; peripheral coldness; nausea/vomiting; and/or respiratory difficulties. Arrhythmias, including fatal ventricular fibrillation, rapid rises in blood pressure producing cerebral hemorrhage, and angina have occurred. ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Adverse Reactions associated with Epinephrine Infusion (for Hypotension associated with Septic Shock) The following adverse reactions associated with the infusion of epinephrine were identified in the literature. 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, myocardial ischemia, myocardial infarction, limb ischemia, pulmonary edema Gastrointestinal disorders: Nausea, vomiting General disorders and administrative site conditions: Chest pain, extravasation Metabolic: hypoglycemia, hyperglycemia, insulin resistance, hypokalemia, lactic acidosis Nervous system disorders: Headache, nervousness, paresthesia, tremor, stroke, central nervous system bleeding Psychiatric disorders: Excitability Renal disorders: Renal insufficiency Respiratory: Pulmonary edema, rales Skin and subcutaneous tissue disorders: Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation 6.2 Adverse Reactions associated with Intramuscular or Subcutaneous Use (for Anaphylaxis) 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 ( 5.9 )]. 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 [see Warnings and Precautions ( 5.6 )] : angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, and ventricular ectopy. Angina may occur in patients with coronary artery disease. 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. Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease. Respiratory: respiratory difficulties. Neurological: dizziness, disorientation, excitability, headache, impaired memory, lightheadedness, nervousness, panic, psychomotor agitation, sleepiness, tingling, tremor, and weakness. Psychiatric: anxiety, apprehensiveness, restlessness.

rly patients with cardiovascular disease. 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. Skin: sweating. Other: Patients with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms [see Warnings and Precautions ( 5.9 )]. Diabetic patients may experience transient increases in blood sugar [see Warnings and Precautions ( 5.9 )]. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions ( 5.3 )]. 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 ( 5.3 )]. 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 ( 5.8 )] . 6.3 Adverse Reactions Associated with Intraocular Use (for Mydriasis) Epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL). Warning is advised [see Warnings and Precautions ( 5.7 )]. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

7 DRUG INTERACTIONS Drugs antagonizing pressor effects of epinephrine • α-blockers, such as phentolamine • Vasodilators, such as nitrates • Diuretics • Antihypertensives • Ergot alkaloids Drugs potentiating pressor effects of epinephrine • Sympathomimetics • β-blockers, such as propranolol • Tricyclic anti-depressants • Monoamine oxidase (MAO) inhibitors • Catechol-O-methyl transferase (COMT) inhibitors, such as entacapone • Clonidine • Doxapram • Oxytocin Drugs potentiating arrhythmogenic effects of epinephrine. Patients who are concomitantly receiving any of the following drugs should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions ( 5.6 ) and Adverse Reactions ( 6 )] . • β-blockers, such as propranolol • Cyclopropane or halogenated hydrocarbon anesthetics, such as halothane • Antihistamines • Thyroid hormones • Diuretics • Cardiac glycosides, such as digitalis glycosides • Quinidine Drugs potentiating hypokalemic effects of epinephrine • Potassium depleting diuretics • Corticosteroids • Theophylline Epinephrine should not be used to counteract circulatory collapse or hypotension caused by phenothiazines, as a reversal of the pressor effects of epinephrine may result in further lowering of blood pressure. Epinephrine may antagonize the neuronal blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter. • Drugs that counter the pressor effects of epinephrine include alpha blockers, vasodilators such as nitrates, diuretics, antihypertensives, and ergot alkaloids. ( 7 ) • Drugs that potentiate the effects of epinephrine include sympathomimetics, beta blockers, tricyclic antidepressants, MAO inhibitors, COMT inhibitors, clonidine, doxapram, oxytocin, levothyroxine sodium, and certain antihistamines. ( 7 ) • Drugs that increase the arrhythmogenic potential of epinephrine include beta blockers, cyclopropane and halogenated hydrocarbon anesthetics, quinidine, antihistamines, exogenous thyroid hormones, diuretics, and cardiac glycosides. Observe for development of cardiac arrhythmias. ( 7 ) • Potassium-depleting drugs, including corticosteroids, diuretics, and theophylline, potentiate the hypokalemic effects of epinephrine. ( 7 )

8 USE IN SPECIFIC POPULATIONS • Pregnancy: May cause fetal harm ( 8.1 ) • Elderly patients and pregnant women may be at greater risk of developing adverse reactions when epinephrine is administered parenterally. ( 8.1 , 8.5 ) 8.1 Pregnancy Risk Summary Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, does not identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus associated with epinephrine use during labor or delivery (see Clinical Considerations ). In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis, resulted in adverse developmental effects (including gastroschisis, embryonic lethality, and delayed skeletal ossification) at doses approximately 2 times the maximum recommended daily intramuscular, subcutaneous, or intravenous dose (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Hypotension associated with septic shock is a medical emergency in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of epinephrine on the fetus. Labor or Delivery Epinephrine usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid epinephrine during the second stage of labor. In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia.

longed period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Data Animal Data In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7, or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for 2 to 3 days). Animals treated on days 6 to 7 had decreased number of implantations. In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10 mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day). 8.2 Lactation Risk Summary There is no information regarding the presence of epinephrine in human milk or the effects of epinephrine on the breastfed infant or on milk production. However, due to its poor oral bioavailability and short half-life, epinephrine exposure is expected to be very low in the breastfed infant. Epinephrine is the first-line medication of choice for treatment of anaphylaxis; it should be used in the same manner for anaphylaxis in breastfeeding and non-breastfeeding patients. 8.4 Pediatric Use Safety and effectiveness of epinephrine in pediatric patients with septic shock have not been established. Clinical use data support weight-based dosing for treatment of anaphylaxis in pediatric patients, and other reported clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. The safety and effectiveness of epinephrine (at a dilution of 1:100,000 to 1:400,000) for induction and maintenance of mydriasis during intraocular surgery have been established in pediatric patients. Use of epinephrine for induction and maintenance of mydriasis during intraocular surgery in pediatric patients is supported by adequate and well controlled studies in adults and uncontrolled studies in pediatric patients. 8.5 Geriatric Use Clinical studies of epinephrine for the treatment of hypotension associated with septic shock did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

fferences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, for the treatment of anaphylaxis, consider starting with a lower dose to take into account potential concomitant disease or other drug therapy. For induction and maintenance of mydriasis during intraocular surgery, no overall differences have been observed between elderly and other patients.

8.1 Pregnancy Risk Summary Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, does not identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus associated with epinephrine use during labor or delivery (see Clinical Considerations ). In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis, resulted in adverse developmental effects (including gastroschisis, embryonic lethality, and delayed skeletal ossification) at doses approximately 2 times the maximum recommended daily intramuscular, subcutaneous, or intravenous dose (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Hypotension associated with septic shock is a medical emergency in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of epinephrine on the fetus. Labor or Delivery Epinephrine usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid epinephrine during the second stage of labor. In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Data Animal Data In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7, or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for 2 to 3 days). Animals treated on days 6 to 7 had decreased number of implantations.

phrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for 2 to 3 days). Animals treated on days 6 to 7 had decreased number of implantations. In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10 mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

8.4 Pediatric Use Safety and effectiveness of epinephrine in pediatric patients with septic shock have not been established. Clinical use data support weight-based dosing for treatment of anaphylaxis in pediatric patients, and other reported clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. The safety and effectiveness of epinephrine (at a dilution of 1:100,000 to 1:400,000) for induction and maintenance of mydriasis during intraocular surgery have been established in pediatric patients. Use of epinephrine for induction and maintenance of mydriasis during intraocular surgery in pediatric patients is supported by adequate and well controlled studies in adults and uncontrolled studies in pediatric patients.

8.5 Geriatric Use Clinical studies of epinephrine for the treatment of hypotension associated with septic shock did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, for the treatment of anaphylaxis, consider starting with a lower dose to take into account potential concomitant disease or other drug therapy. For induction and maintenance of mydriasis during intraocular surgery, no overall differences have been observed between elderly and other patients.

10 OVERDOSAGE Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage may also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency and failure have also been reported. Epinephrine is rapidly inactivated in the body and treatment following overdose is primarily supportive. Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators (such as nitrites) or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

11 DESCRIPTION Epinephrine Injection, USP is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as a 1 mL solution in a single-dose vial. Each mL of Epinephrine Injection, USP solution contains 1 mg epinephrine, sodium chloride 8.6 mg (for isotonicity), sodium metabisulfite 0.25 mg (as preservative), citric acid 0.5 mg and hydrochloric acid for pH adjustment and water for injection, USP, qs. The pH range is 3.0-3.6. Solution must be diluted prior to intravenous or ocular use. Epinephrine is a sympathomimetic catecholamine. The chemical name of epinephrine is: 1,2- Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol. The chemical structure of epinephrine is: The molecular weight of epinephrine is 183.2. Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. epine-sdv-struc-01.jpg

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha (α)- and beta (β)-adrenergic receptors. The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction. 12.2 Pharmacodynamics Intravenous use for hypotension associated with septic shock Following intravenous administration of epinephrine, increases in systolic blood pressure and heart rate are observed. Decreases in systemic vascular resistance and diastolic blood pressure are observed at low doses of epinephrine because of β 2 -mediated vasodilation, but are overtaken by α 1 -mediated peripheral vasoconstriction at higher doses leading to increase in diastolic blood pressure. The onset of blood pressure increase following an intravenous dose of epinephrine is < 5 minutes and the time to offset blood pressure response occurs within 20 min. Most vascular beds are constricted including renal, splanchnic, mucosal and skin. Intramuscular and subcutaneous use for anaphylaxis Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions ( 5.9 )] . Intraocular use for mydriasis Epinephrine causes mydriasis when administered intraocularly or parenterally. 12.3 Pharmacokinetics When administered parenterally or intraocularly, epinephrine has a rapid onset and short duration of action. Following intravenous injection, epinephrine is rapidly cleared from the plasma with an effective half-life of < 5 min. A pharmacokinetic steady state following continuous intravenous infusion is achieved within 10-15 min. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion dose range of 0.03 to 1.7 mcg/kg/min. The extent of human systemic exposure at the labeled intraocular dose has not been evaluated, however, significant systemic concentrations or plasma exposure of epinephrine are not expected when administered intraocularly. Epinephrine is extensively metabolized with only a small amount excreted unchanged. Epinephrine is rapidly degraded to vanillylmandelic acid, an inactive metabolite, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%).

te, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%). Special Populations Elderly In a pharmacokinetic study of 45-minute epinephrine infusions given to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among the older men (144.8 versus 78 mL/kg/min for a 14.3 ng/kg/min infusion). Body Weight Body weight has been found to influence epinephrine pharmacokinetics. Higher body weight was associated with a higher plasma epinephrine clearance and a lower concentration plateau.

12.1 Mechanism of Action Epinephrine acts on both alpha (α)- and beta (β)-adrenergic receptors. The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction.

12.2 Pharmacodynamics Intravenous use for hypotension associated with septic shock Following intravenous administration of epinephrine, increases in systolic blood pressure and heart rate are observed. Decreases in systemic vascular resistance and diastolic blood pressure are observed at low doses of epinephrine because of β 2 -mediated vasodilation, but are overtaken by α 1 -mediated peripheral vasoconstriction at higher doses leading to increase in diastolic blood pressure. The onset of blood pressure increase following an intravenous dose of epinephrine is < 5 minutes and the time to offset blood pressure response occurs within 20 min. Most vascular beds are constricted including renal, splanchnic, mucosal and skin. Intramuscular and subcutaneous use for anaphylaxis Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions ( 5.9 )] . Intraocular use for mydriasis Epinephrine causes mydriasis when administered intraocularly or parenterally.

12.3 Pharmacokinetics When administered parenterally or intraocularly, epinephrine has a rapid onset and short duration of action. Following intravenous injection, epinephrine is rapidly cleared from the plasma with an effective half-life of < 5 min. A pharmacokinetic steady state following continuous intravenous infusion is achieved within 10-15 min. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion dose range of 0.03 to 1.7 mcg/kg/min. The extent of human systemic exposure at the labeled intraocular dose has not been evaluated, however, significant systemic concentrations or plasma exposure of epinephrine are not expected when administered intraocularly. Epinephrine is extensively metabolized with only a small amount excreted unchanged. Epinephrine is rapidly degraded to vanillylmandelic acid, an inactive metabolite, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%). Special Populations Elderly In a pharmacokinetic study of 45-minute epinephrine infusions given to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among the older men (144.8 versus 78 mL/kg/min for a 14.3 ng/kg/min infusion). Body Weight Body weight has been found to influence epinephrine pharmacokinetics. Higher body weight was associated with a higher plasma epinephrine clearance and a lower concentration plateau.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under the Indications and Usage. The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9. 13.2 Animal Toxicology and/or Pharmacology Epinephrine was associated with metabolic effects, decreased mesentery, coronary and renal conductance in a sheep model of septic shock. Data from hemolysis study have shown that epinephrine at 1:1000 dilution is non-hemolytic. Epinephrine infusion significantly increased the MAP (69 vs. 86 mmHg) and cardiac output (6.4 vs. 7.1 L/min) and decreased renal blood flow (330 vs. 247 mL/min).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under the Indications and Usage. The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

13.2 Animal Toxicology and/or Pharmacology Epinephrine was associated with metabolic effects, decreased mesentery, coronary and renal conductance in a sheep model of septic shock. Data from hemolysis study have shown that epinephrine at 1:1000 dilution is non-hemolytic. Epinephrine infusion significantly increased the MAP (69 vs. 86 mmHg) and cardiac output (6.4 vs. 7.1 L/min) and decreased renal blood flow (330 vs. 247 mL/min).

14 CLINICAL STUDIES 14.1 Hypotension associated with Septic Shock Fourteen clinical studies from the literature documented that epinephrine increases the mean arterial pressure (MAP) in patients with hypotension associated with septic shock. 14.2 Induction and Maintenance of Mydriasis during Intraocular Surgery In randomized, controlled studies, patients undergoing routine cataract extraction were evaluated after receiving intraocular irrigation with or without epinephrine diluted up to 1:1,666,666 (0.6 mcg/mL). Patients have also been evaluated after receiving bolus intracameral injections of epinephrine diluted between 1:25,000 (40 mcg/mL) and 1:400,000 (2.5 mcg/mL). In patients with similar pupil diameters at baseline, with or without the use of preoperative mydriatic agents, mydriasis was maintained better in the eyes receiving epinephrine by an average of one to two millimeters in pupil diameter. Pupil constriction to 5 mm or less occurred more often in the patients not receiving epinephrine. Mean pulse rate and blood pressure showed no significance difference between patients receiving epinephrine and controls and there was no increased incidence of ventricular dysrhythmias in patients receiving epinephrine.

16 HOW SUPPLIED/STORAGE AND HANDLING Epinephrine Injection, USP is supplied as follows: Product Code Unit of Sale Strength Each CV696125 NDC 72572-235-25 Unit of 25 1 mg/mL NDC 72572-235-01 1 mL Single-Dose Vial Epinephrine is light sensitive. Protect from light until ready to use. Do not refrigerate. Protect from freezing. Discard unused portion. Store at room temperature, between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.) Protect from alkalis and oxidizing agents. Inspect visually for particulate matter and discoloration prior to administration. Do not use the solution if it is colored or cloudy, or if it contains particulate matter.

<table width="100%"><col width="21%"/><col width="31%"/><col width="24%"/><col width="24%"/><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Product Code</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Unit of Sale</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Strength</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Each</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>CV696125 </paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>NDC 72572-235-25 Unit of 25 </paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>1 mg/mL </paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>NDC 72572-235-01 1 mL Single-Dose Vial </paragraph></td></tr></tbody></table>

17 PATIENT COUNSELING INFORMATION Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine, including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning. Warn patients with a good response to initial treatment about the possibility of recurrence of anaphylaxis symptoms and instruct patients to obtain medical attention if symptoms return. Advise patients with diabetes that they may develop increased blood glucose levels following epinephrine administration. 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 [see Warnings and Precautions ( 5.8 )] . Distributed by: Civica, Inc. Lehi, Utah 84048 U.S Patent 12,539,283 451871 epine-sdv-img-01.jpg

1 INDICATIONS AND USAGE Epinephrine Injection, 0.3 mg are indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. Epinephrine Injection, 0.3 mg are intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions. Anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema. Epinephrine Injection, 0.3 mg are intended for immediate administration as emergency supportive therapy only and are not a substitute for immediate medical care. Epinephrine Injection, 0.3 mg contain epinephrine, are non-selective alpha and beta-adrenergic receptor agonist indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis. ( 1 )

2 DOSAGE AND ADMINISTRATION Patients greater than or equal to 30 kg (66 lbs): Epinephrine injection, 0.3 mg ( 2 ) Patients 15 to 30 kg (33 lbs to 66 lbs): Epinephrine injection, 0.15 mg ( 2 ) Inject intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Each device is a single-dose injection. ( 2 ) 2.1 Recommended Dosage According to Patient Body Weight Patients greater than or equal to 30 kg (approximately 66 pounds or more): Epinephrine injection, 0.3 mg Patients 15 kg to 30 kg (33 pounds to 66 pounds): Epinephrine injection, 0.15 mg 2.2 Administration Instructions Inject the single-dose epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject intravenously, and do not inject into buttocks, into digits, hands or feet [see Warnings and Precautions (5.2)] . Instruct caregivers of young children who are prescribed an epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg and who may be uncooperative and kick or move during an injection to hold the leg firmly in place and limit movement prior to and during an injection [ see Warnings and Precautions (5.2) ]. Each epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg is a single-dose epinephrine injection for single use. Since the doses of epinephrine delivered from epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. With severe persistent anaphylaxis, repeat injections with an additional epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may be necessary. More than two sequential doses of epinephrine should only be administered under direct medical supervision [ see Warnings and Precautions (5.1) ]. The epinephrine solution in the clear window of the Epinephrine Injection 0.3 mg (Auto-Injector) or Epinephrine Injection 0.15 mg (Auto-Injector) should be inspected visually for particulate matter and discoloration. Discarding After Use: The epinephrine injection 0.3 mg each contain 1 mL epinephrine solution. Approximately 0.7 mL remains in the auto-injector after activation, but is not available for future use, and should be discarded.

3 DOSAGE FORMS AND STRENGTHS Injection: 0.3 mg (0.3 mg/0.3 mL), clear and colorless solution in single-dose pre-filled auto-injector Injection: 0.3 mg (0.3 mg/0.3 mL) single-dose pre-filled auto-injector (3)

5 WARNINGS AND PRECAUTIONS In conjunction with use, seek immediate medical or hospital care. ( 5.1 ) Do not inject intravenously, into buttock, or into digits, hands, or feet. ( 5.2 ) To minimize the risk of injection related injury, hold the child’s leg firmly in place and limit movement prior to and during injection when administering to young children. ( 5.2) 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. ( 5.3 ) The presence of a sulfite in this product should not deter use. ( 5.4 ) Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. ( 5.5 ) 5.1 Emergency Treatment Epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are intended for immediate administration as emergency supportive therapy and are not intended as a substitute for immediate medical care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision [ see Indications and Usage ( 1 ), Dosage and Administration ( 2 ) and Patient Counseling Information ( 17 ) ]. 5.2 Injection-Related Complications Epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg should only be injected into the anterolateral aspect of the thigh [ see Dosage and Administration ( 2 ) and Patient Counseling Information ( 17 ) ]. Do not inject intravenously Large doses or accidental intravenous injection of 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. Advise the patient to go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with 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 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. Advise the patient to go immediately to the nearest emergency room and to 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 Lacerations, bent needles, and embedded needles have been reported when epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg have been injected into the thigh of young children who are uncooperative and kick or move during an injection. To minimize the risk of injection related injury when administering, hold the child’s leg firmly in place and limit movement prior to and during injection.

injection, 0.3 mg and epinephrine injection, 0.15 mg have been injected into the thigh of young children who are uncooperative and kick or move during an injection. To minimize the risk of injection related injury when administering, hold the child’s leg firmly in place and limit movement prior to and during injection. 5.3 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 (5.2) ]. 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. 5.4 Allergic Reactions Associated with Sulfite The presence of a sulfite in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive. Epinephrine is the preferred treatment for serious allergic reactions 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. 5.5 Disease Interactions 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, patients with these conditions, and/or any other person who might be in a position to administer epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which epinephrine should be used. Patients with Heart Disease Epinephrine should be administered 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 Drug Interactions (7) and Adverse Reactions (6) ]. Other Patients and Diseases Epinephrine should be administered with caution to patients with hyperthyroidism, diabetes, elderly individuals, and pregnant women. Patients with Parkinson’s disease may notice a temporary worsening of symptoms.

6 ADVERSE REACTIONS 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. Common adverse reactions to systemically administered epinephrine include anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/or respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism [ see Warnings and Precautions ( 5.5 ) ]. Cardiovascular Reactions Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or those receiving certain drugs [ see Warnings and Precautions ( 5.5 ) and Drug Interactions ( 7 ) ]. Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [ see Warnings and Precautions ( 5.5 ) ]. Angina may occur in patients with coronary artery disease [ see Warnings and Precautions ( 5.5 ) ]. Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine. Reactions from Accidental Injection and/or Improper Technique Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [ see Warnings and Precautions ( 5.2 ) ]. Adverse reactions experienced as a result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury. Lacerations, bent needles, and embedded needles have been reported when epinephrine injection has been injected into the thigh of young children who are uncooperative and kick or move during the injection [ see Warnings and Precautions ( 5.2 ) ]. Injection into the buttock has resulted in cases of gas gangrene [ see Warnings and Precautions ( 5.2 ) ]. Skin and Soft Tissue Infections 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, including epinephrine injection 0.3 mg, in the thigh [ see Warnings and Precautions ( 5.3 ) ]. Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS Cardiac Glycosides, Diuretics, and Anti-arrhythmics Patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias [ see Warnings and Precautions ( 5.5 ) ]. Antidepressants, Monoamine Oxidase Inhibitors, Levothyroxine, and Antihistamines The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine. Beta-Adrenergic Blockers The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol. Alpha-Adrenergic Blockers The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine. Ergot Alkaloids Ergot alkaloids may also reverse the pressor effects of epinephrine. Cardiac glycosides or diuretics: observe for development of cardiac arrhythmias. ( 7 ) Tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines potentiate effects of epinephrine. ( 7 ) Beta-adrenergic blocking drugs antagonize cardiostimulating and bronchodilating effects of epinephrine. ( 7 ) Alpha-adrenergic blocking drugs antagonize vasoconstricting and hypertensive effects of epinephrine. ( 7 ) Ergot alkaloids may reverse the pressor effects of epinephrine. ( 7 )

8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 5.5 , 8.5) 8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day). 8.2 Lactation Risk Summary There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients.

n Risk Summary There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients. 8.4 Pediatric Use Epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may be administered to pediatric patients at a dosage appropriate to body weight [ see Dosage and Administration ( 2.1 ) ] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. 8.5 Geriatric Use Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, epinephrine injection, 0.3 mg should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [ see Warnings and Precautions ( 5.5 ), Overdosage ( 10 ) ].

8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk: During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data: In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

8.4 Pediatric Use Epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may be administered to pediatric patients at a dosage appropriate to body weight [ see Dosage and Administration ( 2.1 ) ] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.

8.5 Geriatric Use Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, epinephrine injection, 0.3 mg should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [ see Warnings and Precautions ( 5.5 ), Overdosage ( 10 ) ].

11 DESCRIPTION Epinephrine Injection USP, 0.3 mg are single-dose auto-injectors and combination products containing drug and device components. Each Epinephrine Injection USP, 0.3 mg (Auto-Injector) delivers a single dose of 0.3 mg epinephrine, USP from epinephrine injection USP, 0.3 mg/0.3 mL in a sterile solution. Each 0.3 mL in the Epinephrine Injection USP, 0.3 mg (Auto-Injector) contains 0.3 mg epinephrine USP, 1.8 mg sodium chloride, 0.4 mg sodium metabisulfite, 0.4 mg sodium tartrate (dihydrate), hydrochloric acid to adjust pH, and water for injection. The pH range is 2.2 to 5.0. Epinephrine, USP is a sympathomimetic catecholamine. Chemically, epinephrine, USP is (-)-3,4-Dihydroxy-α-[(methylamino)methyl]benzyl alcohol with the following structure: Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. Replace Epinephrine Injection USP, 0.3 mg if the epinephrine solution appears discolored (pinkish or darker than slightly yellow), cloudy, or if it contains a precipitate. Thoroughly review the patient instructions and operation of Epinephrine Injection USP, 0.3 mg with patients and caregivers prior to use [ see Patient Counseling Information ( 17 ) ]. structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha- and beta-adrenergic receptors. 12.2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage (1)] . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage (1)] . The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Epinephrine Injection USP, 0.3 mg (Auto-Injectors) is supplied with two single-dose pre-filled auto-injectors and one auto-injector trainer device: 0.3 mg/0.3 mL (NDC 85766-091-02 relabeled from NDC 0093-5986-27). Epinephrine Injection USP, 0.3 mg 2-Pack also includes a W-clip to clip two auto-injectors together. Storage and Handling Protect from light. Epinephrine, USP is light sensitive and the auto-injector is manufactured from transparent UV stabilized polycarbonate to protect it from light. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Do not refrigerate. Before using, check to make sure the solution in the auto-injector is clear and colorless. Replace the auto-injector if the solution is discolored (pinkish or darker than slightly yellow), cloudy, or contains a precipitate. Properly dispose all used, unwanted or expired epinephrine injection, 0.3 mg. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information and Instructions for Use) A healthcare provider should review the patient instructions and operation of epinephrine injection, 0.3 mg in detail, with the patient or caregiver. Epinephrine is essential for the treatment of anaphylaxis. Patients who are at risk of or with a history of severe allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, as well as idiopathic and exercise-induced anaphylaxis, should be carefully instructed about the circumstances under which epinephrine should be used. Administration Instruct patients and/or caregivers in the appropriate use of epinephrine injection, 0.3 mg should be injected into the middle of the outer thigh (through clothing, if necessary). Each device is a single-use injection. Advise patients to seek immediate medical care in conjunction with administration of epinephrine injection, 0.3 mg. Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection. Lacerations, bent needles, and embedded needles have been reported when epinephrine injection, 0.3 mg have been injected into the thigh of young children who are uncooperative and kick or move during an injection [ see Warnings and Precautions (5.2) ]. Instruct patients and/or caregivers to throw away the blue safety release immediately after using epinephrine injection, 0.3 mg. This small part may pose a choking hazard for children. Complete patient information, including dosage, directions for proper administration and precautions can be found inside each epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg carton. A printed label on the surface of epinephrine injection, 0.3 mg shows instructions for use and a diagram depicting the injection process. Training Instruct patients and/or caregivers to use and practice with the Trainer to familiarize themselves with the use of epinephrine injection, 0.3 mg in an allergic emergency. The Trainer may be used multiple times. A Trainer device is provided in 2-Pack cartons. Instruct patients and/or caregivers to immediately place the blue safety release back on the Trainer and reset it after practicing. This small part may pose a choking hazard for children. Adverse Reactions Epinephrine may produce symptoms and signs that include an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These signs and symptoms usually subside rapidly, especially with rest, quiet and recumbency. Patients with hypertension or hyperthyroidism may develop more severe or persistent effects, and patients with coronary artery disease could experience angina. Patients with diabetes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms [ see Warnings and Precautions (5.5) ]. Accidental Injection Advise patients to seek immediate medical care in the case of accidental injection. Since epinephrine is a strong vasoconstrictor when injected into the digits, hands, or feet, treatment should be directed at vasodilatation if there is such an accidental injection to these areas [ see Warnings and Precautions (5.2) ].

Advise patients to seek immediate medical care in the case of accidental injection. Since epinephrine is a strong vasoconstrictor when injected into the digits, hands, or feet, treatment should be directed at vasodilatation if there is such an accidental injection to these areas [ see Warnings and Precautions (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 [ see Warnings and Precautions (5.3) ]. Storage and Handling Instruct patients to inspect the epinephrine solution visually through the clear window of the auto-injector periodically. Replace epinephrine injection, 0.3 mg if the epinephrine solution appears discolored (pinkish or darker than slightly yellow), cloudy or if it contains a precipitate. Epinephrine is light sensitive and should be protected from light. The auto-injector is not waterproof. Instruct patients that epinephrine injection, 0.3 mg must be used or properly disposed once the blue safety release is removed or after use [ see Storage and Handling (16.2) ]. Advise patients and caregivers to give used epinephrine injection, 0.3 mg auto-injectors to their healthcare provider for inspection and proper disposal. Advise patients and caregivers to promptly dispose of medicines that are no longer needed. Dispose of expired, unwanted, or unused epinephrine injection, 0.3 mg in an FDA-cleared sharps container. Instruct patients not to dispose epinephrine injection, 0.3 mg in their household trash. Instruct patients that if they do not have a FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Inform patients that they can visit the FDA website for additional information on disposal of unused medicines. Complete patient information, including dosage, directions for proper administration and precautions can be found inside each epinephrine injection, 0.3 mg (Auto-Injector) carton. Distributed by: Sportpharm LLC 379 Van Ness Ave 1401, Torrance, CA 90501 Relabeled by: Enovachem PHARMACEUTICALS Torrance, CA 90501

PATIENT INFORMATION and INSTRUCTIONS FOR USE Epinephrine Injection USP, 0.3 mg (Auto-Injector) Epinephrine Injection USP, 0.3 mg = one dose of 0.3 mg epinephrine USP, 0.3 mg/0.3 mL For allergic emergencies (anaphylaxis) Patient Information Read this Patient Information Leaflet carefully before using the epinephrine injection, 0.3 mg (auto-injector) and each time you get a refill. There may be new information. You, your parent, caregiver, or others who may be in a position to administer epinephrine injection, 0.3 mg (auto-injector), should know how to use it before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about epinephrine injection, 0.3 mg? 1. Epinephrine injection, 0.3 mg are single-dose automatic injection devices (auto-injectors) that contain epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life threatening, can happen within minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or unknown causes. Symptoms of anaphylaxis may include: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth, or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements (incontinence) diarrhea or stomach cramps dizziness, fainting, or “passing out” (unconsciousness) 2. Always carry your epinephrine injection, 0.3 mg with you because you may not know when anaphylaxis may happen. Talk to your healthcare provider if you need additional units to keep at work, school, or other locations. Tell your family members, caregivers, and others where you keep your epinephrine injection, 0.3 mg and how to use it before you need it. You may be unable to speak in an allergic emergency. 3. When you have an allergic emergency (anaphylaxis) Use epinephrine injection, 0.3 mg right away. Get emergency medical help right away. You may need further medical attention. You may need to use a second epinephrine injection, 0.3 mg if symptoms continue or recur. Only a healthcare provider should give additional doses of epinephrine if you need more than 2 injections for a single anaphylaxis episode. What are epinephrine injection, 0.3 mg? Epinephrine injection, 0.3 mg are disposable, pre-filled auto-injectors used to treat life-threatening, allergic emergencies including anaphylaxis in people who are at risk for or have a history of serious allergic emergencies. Each device contains a single dose of epinephrine. Epinephrine injection, 0.3 mg are for immediate self (or caregiver) administration and do not take the place of emergency medical care. You should get emergency help right away after using epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg. Epinephrine injection, 0.3 mg are for people who have been prescribed this medicine by their healthcare provider. The Epinephrine Injection, 0.3 mg (Auto-Injector) is for patients who weigh 66 pounds or more (30 kilograms or more). It is not known if epinephrine injection, 0.3 mg are safe and effective in children who weigh less than 33 pounds (15 kilograms). What should I tell my healthcare provider before using the epinephrine injection, 0.3 mg ?

jection, 0.3 mg (Auto-Injector) is for patients who weigh 66 pounds or more (30 kilograms or more). It is not known if epinephrine injection, 0.3 mg are safe and effective in children who weigh less than 33 pounds (15 kilograms). What should I tell my healthcare provider before using the epinephrine injection, 0.3 mg ? Before you use epinephrine injection, 0.3 mg , tell your healthcare provider about all your medical conditions, but especially if you: have heart problems or high blood pressure. have diabetes. have thyroid problems. have asthma. have a history of depression. have Parkinson’s disease. are pregnant or plan to become pregnant. It is not known if epinephrine will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if epinephrine passes into your breast milk. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your healthcare provider about all of your known allergies. Especially tell your healthcare provider if you take certain asthma medicines. Epinephrine injection, 0.3 mg and other medicines may affect each other, causing side effects. Epinephrine injection, 0.3 mg may affect the way other medicines work, and other medicines may affect how epinephrine injection, 0.3 mg work. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Use your epinephrine injection, 0.3 mg for treatment of anaphylaxis as prescribed by your healthcare provider, regardless of your medical conditions or the medicines you take. How should I use epinephrine injection, 0.3 mg? Each epinephrine injection, 0.3 mg (auto-injector) contains only 1 dose of medicine (single-dose). Epinephrine injection, 0.3 mg Auto-Injectors deliver a fixed dose of epinephrine. The auto-injectors cannot be reused. Do not try to reuse epinephrine injection, 0.3 mg after the device has been activated. It is normal for most of the medicine to remain in the auto-injector after the dose has been injected. The dose has been injected if the orange tip is extended and the window is blocked. Epinephrine injection, 0.3 mg should be injected into the middle of your outer thigh (upper leg). It can be injected through your clothing if needed. Do not inject into a vein or into the buttocks, fingers, toes, hands or feet. Read the Instructions for Use at the end of this Patient Information Leaflet about the right way to use epinephrine injection, 0.3 mg . Your healthcare provider will show you how to safely use the epinephrine injection, 0.3 mg (auto-injector) (auto-injector). Use your single-dose epinephrine injection, 0.3 mg exactly as your healthcare provider tells you to use it. You may need to use a second epinephrine injection, 0.3 mg if symptoms continue or recur. Only a healthcare provider should give additional doses of epinephrine if you need more than 2 injections for a single anaphylaxis episode. Caution: Never put your thumb, fingers, or hand over the orange tip. Never press or push the orange tip with your thumb, fingers, or hand. The needle comes out of the orange tip. Accidental injection into finger, hands or feet may cause a loss of blood flow to these areas. If an accidental injection happens, go immediately to the nearest emergency room. Tell the healthcare provider where on your body you received the accidental injection. Your epinephrine injection, 0.3 mg (auto-injector) may come packaged with an Epinephrine Injection Trainer and separate Epinephrine Injection Trainer Instructions for Use. The Epinephrine Injection Trainer has a grey color. The grey Epinephrine Injection Trainer contains no medicine and no needle.

accidental injection. Your epinephrine injection, 0.3 mg (auto-injector) may come packaged with an Epinephrine Injection Trainer and separate Epinephrine Injection Trainer Instructions for Use. The Epinephrine Injection Trainer has a grey color. The grey Epinephrine Injection Trainer contains no medicine and no needle. Keep the Epinephrine Injection Trainer and the real Epinephrine Injection, 0.3 mg Auto-Injectors away from young children. The real Epinephrine Injection, 0.3 mg and Epinephrine Injection, 0.15 mg Auto-Injectors and Epinephrine Injection Trainer are not toys. For young children, use of the Epinephrine Injection Trainer and the real Epinephrine Injection, 0.3 mg Auto-Injectors should be supervised by an adult. Periodically practice with your Epinephrine Injection Trainer before an allergic emergency happens to make sure you are able to safely use the real epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) in an emergency. Always carry your real epinephrine injection, 0.3 mg (auto-injector) with you in case of an allergic emergency. Additional training resources are available at www.TevaEpinephrine.com . Do not drop the auto-injector. If the auto-injector is dropped, check for damage and leakage. Throw away (dispose of) the auto-injector and replace if damage or leakage is noticed or suspected. What are the possible side effects of epinephrine injection, 0.3 mg? Epinephrine injection, 0.3 mg may cause serious side effects. The epinephrine injection, 0.3 mg should only be injected into the middle of your outer thigh (upper leg). Do not inject the epinephrine injection, 0.3 mg into your: veins buttocks fingers, toes, hands, or feet If you accidentally inject epinephrine injection, 0.3 mg into any other part of your body, go to the nearest emergency room right away. Tell the healthcare provider where on your body you received the accidental injection. Rarely, patients who have used epinephrine injection, 0.3 mg may develop infections at the injection site within a few days of an injection. Some of these infections can be serious. Call your healthcare provider right away if you have any of the following at an injection site: redness that does not go away swelling tenderness the area feels warm to the touch Cuts on the skin, bent needles, and needles that remain in the skin after the injection, have happened in young children who do not cooperate and kick or move during an injection. If you inject a young child with epinephrine injection, 0.3 mg , hold their leg firmly in place before and during the injection to prevent injuries. Ask your healthcare provider to show you how to: Hold the young child firmly in place (restrain). With 1 hand, quickly twist the yellow cap off the Epinephrine Injection, 0.3 mg auto-injector or the green cap off the Epinephrine Injection, 0.15 mg auto-injector in the direction of the “twist arrow” to remove it. Grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. With your other hand, pull off the blue safety release. If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have longer lasting side effects when you use your epinephrine injection, 0.3 mg . Talk to your healthcare provider about all your medical conditions. Common side effects of epinephrine injection, 0.3 mg include: fast, irregular or “pounding” heartbeat sweating headache weakness shakiness paleness feelings of over excitement, nervousness or anxiety dizziness nausea or vomiting breathing problems These side effects may go away with rest. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of the epinephrine injection, 0.3 mg .

ngs of over excitement, nervousness or anxiety dizziness nausea or vomiting breathing problems These side effects may go away with rest. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of the epinephrine injection, 0.3 mg . For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store epinephrine injection, 0.3 mg? Store epinephrine injection, 0.3 mg at room temperature between 68° to 77°F (20° to 25°C). Protect from light. Do not expose to extreme cold or heat. For example, do not store in your vehicle’s glove box and do not store in the refrigerator or freezer. Examine the contents in the clear window of your auto-injector periodically. The solution should be clear. If the solution is discolored (pinkish or darker than slightly yellow) or contains solid particles, replace the unit. Always protect your epinephrine injection, 0.3 mg (auto-injector) from damage and water. The blue safety release helps to prevent accidental injection. Keep the blue safety release on until you need to use epinephrine injection, 0.3 mg . Your epinephrine injection, 0.3 mg has an expiration date. Replace it before the expiration date. Throw away (dispose of) expired, unwanted, or unused epinephrine injection, 0.3 mg in an FDA-cleared sharps disposal container. Do not throw away the epinephrine injection, 0.3 mg in your household trash. If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: Made of heavy-duty plastic, Can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, Upright and stable during use, Leak-resistant, and Properly labeled to warn of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal Visit the FDA’s website (https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know) for more information about how to throw away (dispose of) unused, unwanted or expired medicines. Keep epinephrine injection, 0.3 mg and all medicines out of the reach of children. General information about the safe and effective use of epinephrine injection, 0.3 mg Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use the epinephrine injection, 0.3 mg for a condition for which it was not prescribed. Do not give your epinephrine injection, 0.3 mg to other people. This Patient Information Leaflet summarizes the most important information about epinephrine injection, 0.3 mg. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about epinephrine injection, 0.3 mg that is written for health professionals. For more information and video instructions on the use of epinephrine injection, 0.3 mg go to www.TevaEpinephrine.com or call 1-888-838-2872. What are the ingredients in epinephrine injection, 0.3 mg? Active Ingredients : Epinephrine Inactive Ingredients: sodium chloride, sodium metabisulfite, sodium tartrate (dihydrate), hydrochloric acid, and water Important Information The Epinephrine Injection, 0.3 mg (Auto-Injector) has a yellow colored label.

838-2872. What are the ingredients in epinephrine injection, 0.3 mg? Active Ingredients : Epinephrine Inactive Ingredients: sodium chloride, sodium metabisulfite, sodium tartrate (dihydrate), hydrochloric acid, and water Important Information The Epinephrine Injection, 0.3 mg (Auto-Injector) has a yellow colored label. The Epinephrine Injection Trainer has a grey color and contains no medicine and no needle. Your auto-injector is designed to work through clothing. The blue safety release on the Epinephrine Injection, 0.3 mg (Auto-Injector) helps to prevent accidental injection of the device. Do not remove the blue safety release until you are ready to use it. Choking hazard: The blue safety release is a small part that may become a choking hazard for children. Throw away the blue safety release immediately after using epinephrine injection, 0.3 mg. Only inject into the middle of the outer thigh (upper leg). Never inject into any other part of the body. Never put your thumb, fingers, or your hand over the orange tip. The needle comes out of the orange tip. If an accidental injection happens, get emergency medical help right away. INSTRUCTIONS FOR USE Epinephrine Injection USP, 0.3 mg (Auto-Injector) Epinephrine Injection USP, 0.3 mg = one dose of 0.3 mg epinephrine USP, 0.3 mg/0.3 mL For allergic emergencies (anaphylaxis) Read this Instructions for Use carefully before you use epinephrine injection, 0.3 mg . Before you need to use your single-dose epinephrine injection, 0.3 mg auto-injector, make sure your healthcare provider shows you the right way to use it. Parents, caregivers, and others who may be in a position to administer epinephrine injection, 0.3 mg (auto-injector) should also understand how to use it as well. If you have any questions, ask your healthcare provider. Your Epinephrine Injection, 0.3 mg (Auto-Injector) A dose of epinephrine injection, 0.3 mg requires 3 steps: Prepare, Administer and Get emergency medical help Step 1. Prepare epinephrine injection, 0.3 mg for injection Quickly twist the yellow cap off the epinephrine injection, 0.3 mg auto-injector in the direction of the “twist arrow” to remove it. Grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. With your other hand, pull off the blue safety release. Important: The blue safety release is a small part that may become a choking hazard for children. Throw away the blue safety release immediately after using epinephrine injection, 0.3 mg . Note: The needle comes out of the orange tip. To avoid an accidental injection, never put your thumb, fingers or hand over the orange tip. If an accidental injection happens, get emergency medical help right away. Step 2. Administer epinephrine injection, 0.3 mg If you are administering epinephrine injection, 0.3 mg to a young child, hold the leg firmly in place while administering an injection. Place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. Swing and push the auto-injector firmly until it ‘clicks’. The click signals that the injection has started. Hold firmly in place for 3 seconds (count slowly 1,2,3). The injection is now complete. Remove the auto-injector from the thigh. The orange tip will extend to cover the needle. If the needle is still visible, do not attempt to reuse it. Massage the injection area for 10 seconds. Step 3. Get emergency medical help now. You may need further medical attention. You may need to use a second epinephrine injection, 0.3 mg (auto-injector) (auto-injector) if symptoms continue or recur. Take your used auto-injector with you when you go to see a healthcare provider. Tell the healthcare provider that you have received an injection of epinephrine.

u may need further medical attention. You may need to use a second epinephrine injection, 0.3 mg (auto-injector) (auto-injector) if symptoms continue or recur. Take your used auto-injector with you when you go to see a healthcare provider. Tell the healthcare provider that you have received an injection of epinephrine. Show the healthcare provider where you received the injection. Give your used epinephrine injection, 0.3 mg (auto-injector) (auto-injector) to the healthcare provider for inspection and proper disposal. Ask for a refill, if needed. Note: Keep the Epinephrine Injection Trainer and the real epinephrine injection, 0.3 mg away from young children. The real epinephrine injection, 0.3 mg and Epinephrine Injection Trainer are not toys. For young children, use of the Epinephrine Injection Trainer and the real epinephrine injection, 0.3 mg Auto-Injectors should be supervised by an adult. A carrying tube is not provided as seen with other products. Epinephrine injection, 0.3 mg are single-dose injectable devices that deliver a fixed dose of epinephrine. The auto-injector cannot be reused. Do not attempt to reuse epinephrine injection after the device has been activated. It is normal for most of the medicine to remain in the auto-injector after the dose is injected. The correct dose has been administered if the orange needle tip is extended and the window is blocked. Your epinephrine injection, 0.3 mg (auto-injector) may come packaged with an Epinephrine Injection Trainer and separate Epinephrine Injection Trainer Instructions for Use. The Epinephrine Injection Trainer has a grey color. The grey Epinephrine Injection Trainer contains no medicine and no needle. Practice with your Epinephrine Injection Trainer, but always carry your real epinephrine injection, 0.3 mg auto-injector in case of an allergic emergency. If you are administering epinephrine injection, 0.3 mg to a young child, ask your healthcare provider to show you how to (1) hold the young child firmly in place (restrain), (2) with 1 hand, quickly twist the yellow cap off the epinephrine injection, 0.3 mg (auto-injector) in the direction of the “twist arrow” to remove it, (3) grasp the auto-injector in your fist with the orange tip (needle end) pointing downward and (4) with your other hand, pull off the blue safety release, and how to properly hold the leg in place while administering a dose. Do not try to take the epinephrine injection, 0.3 mg (auto-injector) apart. This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Distributed by: Sportpharm 2237 N Commerce Parkway, STE 1, Weston, Florida-33326 Relabeled by: Enovachem PHARMACEUTICALS Torrance, CA 90501 Epinephrine Injection USP, 0.3 mg (Auto-Injector) Epinephrine Injection USP, 0.3 mg = one dose of 0.3 mg epinephrine USP, 0.3 mg/0.3 mL TevaEpinephrine.com Register your Epinephrine Injection 0.3 mg (Auto-Injector) at www.TevaEpinephrine.com and find out more about: Free Epinephrine Injection Auto-Injector Refill Reminder Program . It is important to keep your auto-injector up-to-date. Register up to 6 Epinephrine Injection 0.3 mg (Auto-Injectors) and receive automatic Refill Reminder Alerts. Receive periodic information related to allergies and allergens. Instructional Video For more information about Epinephrine Injection 0.3 mg (Auto-Injector) and proper use of the products, call Teva at 1-888-838-2872 or visit www.TevaEpinephrine.com . Epinephrine Injection Trainer Instructions for Use In an emergency: Do not use the grey Trainer. Use your real yellow Epinephrine Injection 0.3 mg Auto-Injector or real green Epinephrine Injection 0.15 mg Auto-Injector. Important Information The Trainer label has a grey color.

38-2872 or visit www.TevaEpinephrine.com . Epinephrine Injection Trainer Instructions for Use In an emergency: Do not use the grey Trainer. Use your real yellow Epinephrine Injection 0.3 mg Auto-Injector or real green Epinephrine Injection 0.15 mg Auto-Injector. Important Information The Trainer label has a grey color. The Trainer contains no medicine and no needle. Keep the grey Trainer away from young children. The Trainer is not a toy. Young children should only practice with the Trainer under adult supervision. Periodically practice with the grey Trainer before an allergic emergency (anaphylaxis) happens to make sure you are able to safely use the real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector in case of an emergency. Always carry your real yellow epinephrine injection 0.3 mg auto-injector in case of an allergic emergency. Small parts like the blue safety release may become a choking hazard for children. Put the blue safety release back on the Trainer and reset it immediately after practicing. The Epinephrine Injection Trainer Familiarize yourself with this grey Trainer. Practice until you are comfortable using it. Your grey Trainer: • Never put your thumb, other fingers, or hand over the orange tip (below grey safety cap). • The orange tip is where the needle comes out of your epinephrine injection 0.3 mg auto-injector. Practice Instructions 1 Prepare the Trainer for Simulated Injection Grasp the grey Trainer in your fist with the orange tip pointing downward and twist off Grey Cap in the direction of “twist arrow”. With your other hand, pull off blue safety release . Removing the blue safety release unlocks the Trainer. 2 Administer the Trainer Simulation If practicing with a young child, hold the leg firmly in place while using the Epinephrine Injection Trainer. Ask your healthcare provider to show you how to: 1. Hold the young child firmly in place (restrain). 2. With 1 hand, quickly twist the grey cap off the Epinephrine Injection Trainer in the direction of the “twist arrow” to remove it. 3. Grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. 4. With your other hand, pull off the blue safety release, and how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. Place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. Swing and push the Trainer firmly until it ‘clicks’. The click signals that the injection has started. Hold firmly in place for 3 seconds (count slowly 1,2,3). Remove the Trainer from the thigh and massage the injection area for 10 seconds. The orange tip automatically extends out after use. Note: In an actual emergency, you would need to seek emergency medical help right away. The actual auto-injector is made to work through clothing. Do not inject into any other part of the body. 3 To reset the Trainer Put the blue safety release back on the Trainer. Replace Grey Cap. NOTE: With the real yellow Epinephrine Injection 0.3 mg Auto-Injector, the orange tip covers the needle after self-injection to help protect you from accidentally sticking yourself or others. Practice Session Information In case of an allergic emergency, use the real yellow Epinephrine Injection 0.3 mg Auto-Injector and not the grey Trainer. Follow instructions above. Repeat as often as needed until you are able to self-inject quickly and correctly.

protect you from accidentally sticking yourself or others. Practice Session Information In case of an allergic emergency, use the real yellow Epinephrine Injection 0.3 mg Auto-Injector and not the grey Trainer. Follow instructions above. Repeat as often as needed until you are able to self-inject quickly and correctly. Reread: The Trainer Instructions for Use The “Patient Information” that comes with your Epinephrine Injection 0.3 mg Auto-Injector Train others who could help you in an emergency: • Your parents, caregivers, and others who may be in a position to administer epinephrine injection 0.3 mg or should know how to help you during an allergic emergency (anaphylaxis). Before an emergency occurs, have them: Practice activating the Trainer Read these Trainer Instructions and the “Patient Information” For more information about the Epinephrine Injection 0.3 mg Auto-Injector and the proper use of the products, go to www.TevaEpinephrine.com . Caution: Important differences between the Trainer and your real yellow Epinephrine Injection 0.3 mg (Auto-Injector) Trainer (Grey) Epinephrine Injection 0.3 mg (Yellow) Contains medicine? No Yes Has needle? No Yes Comes in Carrier Tube? No No Color of label Grey Yellow Has expiration date? No Yes Can be reused? Yes No (use only one time) Okay to remove and replace cap and/or safety release? Yes No (remove just one time before use) Pressure needed to hold against thigh? Moderate Strong This Trainer Instructions for Use has been approved by the U.S. Food and Drug Administration. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Distributed by: Sportpharm LLC 379 Van Ness Ave 1401, Torrance, CA 90501 Relabeled by: Enovachem PHARMACEUTICALS Torrance, CA 90501 ppi image ppi ifu image 1 ppi ifu image 2 1 1 1 1 trainer-ifu image 1 1 1 1 1 0.3 mg injector

<table><colgroup><col width="242px"/><col width="507px"/></colgroup><tbody><tr><td><renderMultiMedia referencedObject="MM3"/></td><td><paragraph>Quickly twist the yellow cap off the epinephrine injection, 0.3 mg auto-injector in the direction of the &#x201C;twist arrow&#x201D; to remove it.</paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM4"/></td><td><paragraph><content styleCode="bold">Grasp the auto-injector in your fist with the orange tip (needle end) pointing downward.</content>With your other hand, <content styleCode="bold">pull off the blue safety release.</content></paragraph></td></tr></tbody></table> <table><colgroup><col width="213px"/><col width="536px"/></colgroup><tbody><tr><td><renderMultiMedia referencedObject="MM5"/></td><td><paragraph>Place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. <content styleCode="bold">Swing and push the auto-injector firmly </content>until it &#x2018;clicks&#x2019;. </paragraph><paragraph>The click signals that the injection has started.</paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM6"/></td><td><paragraph><content styleCode="bold">Hold firmly in place for 3 seconds (count slowly 1,2,3).</content>The injection is now complete. </paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM7"/></td><td><paragraph><content styleCode="bold">Remove the auto-injector from the thigh. </content>The orange tip will extend to cover the needle. If the needle is still visible, do not attempt to reuse it. </paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM8"/></td><td><paragraph>Massage the injection area for 10 seconds.</paragraph></td></tr></tbody></table> <table><colgroup><col width="100px"/></colgroup><tbody><tr styleCode="First Last"><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph>Practice Instructions</paragraph></td></tr></tbody></table>

<table><colgroup><col width="213px"/><col width="536px"/></colgroup><tbody><tr><td><renderMultiMedia referencedObject="MM5"/></td><td><paragraph>Place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. <content styleCode="bold">Swing and push the auto-injector firmly </content>until it &#x2018;clicks&#x2019;. </paragraph><paragraph>The click signals that the injection has started.</paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM6"/></td><td><paragraph><content styleCode="bold">Hold firmly in place for 3 seconds (count slowly 1,2,3).</content>The injection is now complete. </paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM7"/></td><td><paragraph><content styleCode="bold">Remove the auto-injector from the thigh. </content>The orange tip will extend to cover the needle. If the needle is still visible, do not attempt to reuse it. </paragraph></td></tr><tr><td><renderMultiMedia referencedObject="MM8"/></td><td><paragraph>Massage the injection area for 10 seconds.</paragraph></td></tr></tbody></table> <table><colgroup><col width="100px"/></colgroup><tbody><tr styleCode="First Last"><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph>Practice Instructions</paragraph></td></tr></tbody></table> <table><colgroup><col width="30px"/><col width="320px"/><col width="394px"/></colgroup><tbody><tr><td/><td><renderMultiMedia referencedObject="MM10"/></td><td><paragraph>1 <content styleCode="bold">Prepare </content>the Trainer for Simulated Injection </paragraph><list listType="unordered"><item><content styleCode="bold">Grasp the grey Trainer in your fist with the orange tip pointing downward </content>and twist off Grey Cap in the direction of &#x201C;twist arrow&#x201D;. </item><item>With your other hand, <content styleCode="bold">pull off blue safety release</content>. </item><item>Removing the blue safety release unlocks the Trainer.</item></list></td></tr><tr><td/><td/><td><paragraph>2 <content styleCode="bold">Administer </content>the Trainer Simulation </paragraph></td></tr><tr><td/><td colspan="2"><list listType="unordered"><item><content styleCode="bold">If practicing with a young child, hold the leg firmly in place while using the Epinephrine Injection Trainer.</content>Ask your healthcare provider to show you how to: <paragraph>1. Hold the young child firmly in place (restrain).</paragraph><paragraph>2. With 1 hand, quickly twist the grey cap off the Epinephrine Injection Trainer in the direction of the &#x201C;twist arrow&#x201D; to remove it.</paragraph><paragraph>3. Grasp the auto-injector in your fist with the orange tip (needle end) pointing downward.</paragraph><paragraph>4. With your other hand, pull off the blue safety release, and how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens.</paragraph></item></list></td></tr><tr><td/><td><renderMultiMedia referencedObject="MM11"/><renderMultiMedia referencedObject="MM12"/></td><td><list listType="unordered"><item>Place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh.</item><item><content styleCode="bold">Swing and push the Trainer firmly </content>until it &#x2018;clicks&#x2019;. The click signals that the injection has started. </item><item><content styleCode="bold">Hold firmly in place for 3 seconds (count slowly 1,2,3).</content></item><item><content styleCode="bold">Remove the Trainer from the thigh </content>and massage the injection area for 10 seconds. The orange tip automatically extends out after use. </item></list><paragraph>Note:</paragraph><list listType="unordered"><item>In an actual emergency, you would need to seek emergency medical help right away.</item><item>The actual auto-injector is made to work through clothing.</item><item>Do not inject into any other part of the body.</item></list></td></tr><tr><td/><td><renderMultiMedia referencedObject="MM13"/></td><td rowspan="2"><paragraph>3 <content styleCode="bold">To reset </content>the Trainer </paragraph><list listType="unordered"><item>Put the blue safety release back on the Trainer.</item><item>Replace Grey Cap.</item></list></td></tr><tr><td/><td/></tr></tbody></table>

<td><renderMultiMedia referencedObject="MM13"/></td><td rowspan="2"><paragraph>3 <content styleCode="bold">To reset </content>the Trainer </paragraph><list listType="unordered"><item>Put the blue safety release back on the Trainer.</item><item>Replace Grey Cap.</item></list></td></tr><tr><td/><td/></tr></tbody></table> <table><colgroup><col width="141px"/></colgroup><tbody><tr styleCode="First Last"><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Practice Session Information</content></paragraph></td></tr></tbody></table>

<td><renderMultiMedia referencedObject="MM13"/></td><td rowspan="2"><paragraph>3 <content styleCode="bold">To reset </content>the Trainer </paragraph><list listType="unordered"><item>Put the blue safety release back on the Trainer.</item><item>Replace Grey Cap.</item></list></td></tr><tr><td/><td/></tr></tbody></table> <table><colgroup><col width="141px"/></colgroup><tbody><tr styleCode="First Last"><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Practice Session Information</content></paragraph></td></tr></tbody></table> <table><colgroup><col width="94px"/><col width="200px"/><col width="209px"/><col width="232px"/></colgroup><tbody><tr><td rowspan="2" styleCode="Botrule Lrule Rrule Toprule"/><td align="center" styleCode="Botrule Lrule Rrule Toprule"><renderMultiMedia referencedObject="MM14"/></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><renderMultiMedia referencedObject="MM15"/></td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Trainer</content></paragraph><paragraph><content styleCode="bold">(Grey)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Epinephrine Injection 0.3 mg</content></paragraph><paragraph><content styleCode="bold">(Yellow)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Contains medicine?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Has needle?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Comes in Carrier Tube?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Color of label</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Grey</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yellow</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Has expiration date?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Can be reused?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No (use only one time)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule"><paragraph><content styleCode="bold">Okay to remove and replace cap and/or safety release?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No (remove just one ti

to remove and replace cap and/or safety release?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Yes</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">No (remove just one ti me</content></paragraph><paragraph><content styleCode="bold">before use)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Pressure needed to hold against thigh?</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Moderate</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph><content styleCode="bold">Strong</content></paragraph></td></tr></tbody></table>