Auvi-Q

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.

The recommended dosage of AUVI-Q is based on weight. Administer AUVI-Q intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. 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. 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. See full prescribing information for administration instructions.

2.1Recommended 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.

2.2Administration 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 . 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 . 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.

Do not inject intravenously, into buttock, digits, hands, or feet. 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. 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. Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. May aggravate certain coexisting conditions. The presence of a sulfite in this product should not deter use.

5.1Injection-Related Complications

AUVI-Q should only be injected into the anterolateral aspect of the thigh . 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 . 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.

5.2Serious 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 . 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.

5.3Risk 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 . 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.

5.4Allergic 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.

None. None.

8.1Pregnancy 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 . 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 . 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).

The following clinically significant adverse reactions are described elsewhere in the labeling: Injection-Related Complications Serious Infections at the Injection Site Risks Associated with Use of Epinephrine in Certain Coexisting Conditions Allergic Reactions Associated with Sulfite 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.

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 .