AUVI-Q

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

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 )

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.

None. None. ( 4 )

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 .

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.