Auvi-Q (Page 3 of 5)

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 and to be an oxidative mutagen in a WP2 bacterial reverse mutation assay.

Epinephrine was positive in the DNA Repair test with B. subtilis (REC) assay, but was not mutagenic in the Salmonella bacterial reverse mutation assay.

The potential for epinephrine to impair fertility has not been evaluated.

This should not prevent the use of epinephrine under the conditions noted under INDICATIONS AND USAGE ( 1) .

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 HOW SUPPLIED

Carton containing two AUVI-Q (epinephrine injection, USP) 0.3 mg auto-injectors and a single AUVI-Q Trainer — NDC 60842-023-01

Carton containing two AUVI-Q (epinephrine injection, USP) 0.15 mg auto-injectors and a single AUVI-Q Trainer — NDC 60842-022-01

Carton containing two AUVI-Q (epinephrine injection, USP) 0.1 mg auto-injectors and a single AUVI-Q Trainer — NDC 60842-021-01

Rx only

16.2 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°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, cloudy, or contains particles.

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 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-use 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. 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 STORAGE AND HANDLING ( 16.2) ].

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.kaleopharma.com/pat for details.

*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® (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?

1. 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
2. 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.
3. 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.
• 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.
• A Trainer for AUVI-Q with a separate Trainer Instructions for Use leaflet is included with 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 make sure you are able to safely use the real AUVI-Q in an 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 expose to extreme heat or cold. For example, do NOT store in your vehicle’s glove box. Do not store AUVI-Q in the refrigerator or freeze.
• 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. 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 1-844-828-8472.

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.