Anaphylaxis, Food Allergies and EpiPen (epinephrine) Auto-Injector: Frequently Asked Questions

Transcription

1 1 Table of Contents Anaphylaxis Overview Food Allergy-Induced Anaphylaxis About EpiPen (epinephrine) Auto-Injector and EpiPen Jr (epinephrine) Auto-Injector Anaphylaxis Q: What is anaphylaxis? A: Anaphylaxis (a-na-fi-lax-is) is a life-threatening allergic reaction that is rapid in onset and may cause death, 1 either through swelling that shuts off airways or through a significant drop in blood pressure. 2 Q: What are the common signs and symptoms of anaphylaxis? A: According to a 2010 article published in The Journal of Allergy and Clinical Immunology, during anaphylaxis symptoms can range from mild to severe and may affect: 2 Skin (up to 90% of episodes): hives (urticaria), itching (pruritus), flushing, itching and swelling of lips, tongue, uvula/palate 2,3,4,5,6 Airway (up to 70% of episodes): shortness of breath, chest tightness, wheezing, itchy throat, hoarseness (dysphonia) 2,4,5,6 Gastrointestinal system (up to 45% of episodes): nausea, cramping, abdominal pain, vomiting, diarrhea 2,4,5,6 Cardiovascular system (up to 45% of episodes): hypotension, chest pain, fast heart rate (tachycardia), weak pulse, dizziness, fainting 2,4,5,6 Central nervous system (up to 15% of episodes): feelings of uneasiness, throbbing headache, dizziness, confusion, tunnel vision 2,5 Q: How quickly do symptoms appear? A: Symptoms typically appear within minutes to a few hours following contact with an allergen. 1,7 Q: How many Americans are at risk for anaphylaxis? A: Though data on anaphylaxis incidence and prevalence are sparse and often imprecise, estimates indicate that anaphylaxis is a growing health problem that may affect 3 to 43 million Americans. There has been an increase in life-threatening allergic reactions in recent years, but as evidence by the range provided, more research needs to be conducted. 8 Indications EpiPen (epinephrine) 0.3 mg and EpiPen Jr (epinephrine) 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. Important Safety Information EpiPen Auto-Injectors contain a single dose of epinephrine, which you inject into your outer thigh. DO NOT INJECT INTO YOUR VEIN, BUTTOCK, FINGERS, TOES, HANDS OR FEET. In case of accidental injection, please seek immediate medical treatment. Epinephrine should be used with caution if you have heart disease or are taking certain medicines that can cause heart-related (cardiac) symptoms. Please see additional Important Safety Information on next page.

2 2 Q: How many people in the U.S. die from anaphylaxis each year? A: Estimates indicate that anaphylaxis results in up to 1,500 deaths annually in the U.S. 8 Q: How many emergency department visits occur annually as a result of anaphylaxis in the U.S.? A: A study published in the March 2011 issue of The Journal of Allergy and Clinical Immunology stated that anaphylaxis results in approximately 90,000 annual emergency department visits in the U.S. for food allergies alone. 9 Q: How do people know if they are at risk for anaphylaxis? A. Anyone can develop a life-threatening allergy at any time in life, but certain factors may increase the potential to experience anaphylaxis. These include: 2 History of a previous (mild or moderate) allergic reaction Age (adolescents and young adults) History of asthma or other chronic respiratory diseases Ischemic heart disease Medications Immunotherapy (allergy shots) Severe allergic rhinitis or eczema It is important to note that only a health care professional can determine an individual s potential to experience a life-threatening allergic reaction, or anaphylaxis. Q: Are some episodes of anaphylaxis more severe than others for the same person? A: The potential to experience an anaphylactic reaction is based on many factors and cannot always be determined from previous allergic reactions. For example, studies of individuals with peanut allergies have shown that 44-59% of mild allergic reactions may be followed by a severe reaction after a second exposure to the same allergen. 10,11 Q: How are people tested for anaphylaxis triggers? A: In individuals who have experienced anaphylaxis, it is important to confirm the trigger(s). Several tests are available to help identify triggers of anaphylaxis: Skin Tests identify allergies which may be a trigger for anaphylatic reactions such as food, medications and stinging insects. In the case of a skin prick/puncture test, a positive result is indicated by the size of an inflammation when compared to placebo. 2 In Vitro Tests determine the presence of allergen-specific antibody levels and identify anaphylactic reactions triggered by food, stinging insect venom, medications and natural rubber latex. 6 Challenge Tests are incremental health care professional-monitored tests to determine the clinical relevance of positive allergen skin tests or in vitro tests. 12 Important Safety Information (cont d...) Tell your doctor if you have certain medical conditions such as asthma, depression, thyroid disease, Parkinson s disease, diabetes, high blood pressure and heart disease, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell your doctor all the medicines you take, especially medicines for asthma. 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 take the EpiPen or EpiPen Jr Auto Injector. Please see additional Important Safety Information on next page.

3 3 Q: How are people treated for anaphylaxis? A: According to food allergy guidelines released in December 2010 by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), epinephrine is the only first-line treatment in all cases of anaphylaxis (including from food allergies) and should be available at all times to people at risk for anaphylaxis. 3 Avoidance of allergic triggers is the critical first step to prevent a serious health emergency; however, accidental exposure may still happen. 6,13 According to NIAID, if experiencing anaphylaxis, use an epinephrine auto-injector and seek immediate emergency medical attention. 3 Carrying an epinephrine auto-injector does not prevent patients from having an anaphylactic reaction; hence, patients must avoid their allergen at all times. 3,6,14 Q: When should epinephrine be administered? A: Epinephrine is the only first-line treatment in all cases of anaphylaxis (including from food allergies). 3 If experiencing anaphylaxis, use an epinephrine auto-injector and seek immediate emergency medical attention. 3 Anaphylaxis occurs when an allergic reaction involves one body system, either respiratory or cardiovascular alone; it may also occur in multiple body systems, such as the skin, gastrointestinal, and/or central nervous system. 1 It is important to carry an epinephrine autoinjector if you have been diagnosed with life-threatening allergies. Carrying an epinephrine auto-injector does not prevent patients from having an anaphylactic reaction; hence, patients must avoid their allergen at all times. 3,6,14 It is important to remember that the benefits of epinephrine treatment outweigh the risks of delayed or no administration. Delays in epinephrine administration have been associated with negative health consequences, even possibly death. 15,16,17 Since there are no absolute contraindications to epinephrine administration for an anaphylactic reaction, it is important to administer epinephrine immediately even if all criteria for anaphylaxis diagnosis have not yet been met. 5 Q: How many doses of epinephrine are recommended for an individual to have on hand? A: Epinephrine takes effect within minutes, but it is rapidly metabolized. As a result, its effect can be short-lived and repeated dosing may be necessary. In fact, according to a 2005 literature review published in the Annals of Allergy, Asthma & Immunology, up to 20% of individuals who receive epinephrine will require more than one dose before symptoms are alleviated. 18 The NIAID food allergy guidelines recommend that all patients at risk for or who have experienced anaphylaxis have access to two doses of epinephrine at all times. 3 Seek immediate medical attention after use. Q: Are antihistamines a viable treatment option for anaphylaxis? A: Antihistamines are not indicated to treat the life-threatening symptoms of anaphylaxis. Antihistamines are useful for relieving itching and hives. They do not relieve shortness of breath, wheezing, gastrointestinal symptoms or shock. Therefore, antihistamines should be considered adjunctive therapy and should not be substituted for epinephrine. 3 Despite these facts, the use of antihistamines is the most common reason reported for not using epinephrine and may place a patient at significantly increased risk for progression toward a life-threatening allergic reaction. 19 Important Safety Information (cont d...) The most common side effects may include increase in heart rate, stronger or irregular heartbeat, sweating, nausea and vomiting, difficulty breathing, paleness, dizziness, weakness or shakiness, headache, apprehension, nervousness or anxiety. These side effects usually go away quickly, especially if you rest. Talk to your health care professional to see if EpiPen or EpiPen Jr Auto-Injector is right for you. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA-1088.

4 4 Food Allergy-Induced Anaphylaxis Q: What happens when a person has a life-threatening allergic reaction to food? A: Food allergy-induced anaphylaxis occurs when the immune system is exposed to a specific food that triggers the release of chemicals, including histamine, resulting in symptoms of a life-threatening allergic reaction. 3 Symptoms may include low blood pressure, difficulty in breathing, nausea and/or vomiting. 2 Q: How many Americans have food allergies? A: While the exact prevalence of food allergies is uncertain, a 2010 study in The Journal of Allergy and Clinical Immunology estimated 2.5% of Americans have a clinical food allergy. 20 A study in the July 2011 issue of Pediatrics found that 8% of children suffer from a food allergy a considerable increase from previously reported figures. 21 Q: Is there a cure for food allergies? A: There is no cure for food allergies. Avoidance of allergic triggers is the critical first step to prevent a serious health emergency; however, accidental exposure may still happen. 6,13 In fact, cross-contamination of otherwise safe foods at the time of packaging or food preparation (especially in restaurants) remains a potential hazard for individuals with food allergies. 22 This is why it is important to be prepared with an anaphylaxis action plan, which includes avoiding known allergens, recognizing symptoms and having access to two epinephrine auto-injectors. 1,12,23 Q: Are food allergies on the rise? A: The Centers for Disease Control and Prevention reported in 2008 that an 18% increase in food allergy was seen between 1997 and A study published in the July 2011 issue of Pediatrics found a considerable increase in food allergy from previously reported figures it found that 8% of children in the U.S., or approximately one out of 13, suffer from a food allergy. Of those children affected, 38% had a history of a severe reaction, and 30% had allergies to multiple foods. 21 The prevalence of peanut allergies among children under 18 significantly increased from 0.4% in 1997 to 1.4% in 2008 (p < ). 25 Q: How many children are at risk for anaphylaxis from food allergies? A: A study published in the July 2011 issue of Pediatrics found that an estimated one out of 13 children in the U.S. suffer from a food allergy, a considerable increase from previously reported figures. 21 A survey conducted in 109 Massachusetts school districts from 2001 to 2003 evaluating the use of epinephrine for anaphylaxis management in schools found that up to 24% of anaphylactic reactions occurred in individuals who were not known by school personnel to have a prior history of life-threatening allergies. 26 Indications EpiPen (epinephrine) 0.3 mg and EpiPen Jr (epinephrine) 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. Important Safety Information EpiPen Auto-Injectors contain a single dose of epinephrine, which you inject into your outer thigh. DO NOT INJECT INTO YOUR VEIN, BUTTOCK, FINGERS, TOES, HANDS OR FEET. In case of accidental injection, please seek immediate medical treatment. Epinephrine should be used with caution if you have heart disease or are taking certain medicines that can cause heart-related (cardiac) symptoms. Please see additional Important Safety Information on next page.

5 5 Q: What is causing the increase in food allergies? A: There is no definitive answer as to why food allergies are increasing. One theory, called the hygiene hypothesis, suggests that modern hygienic processes and a generally more sterile environment have reduced exposure to certain bacteria. To compensate, the immune system is conditioned toward an allergic state. 13 Q: Can the severity of food allergy-induced anaphylaxis be predicted based on a person s prior reactions? A: The severity of food allergy-induced anaphylaxis cannot be predicted based on a person s prior reactions. An estimated 22% of people who experience fatal food-induced anaphylaxis have had a previous severe reaction. 27 The severity of a food-triggered life-threatening allergic reaction depends on a number of factors, including the amount eaten, the food form (cooked, raw or processed) and the co-ingestion of other foods. Other considerations include the person s age, the body s sensitivity at time of ingestion, the speed at which food is absorbed by the body, and whether the person has another life-threatening condition, such as severe or uncontrolled asthma. 22 Q: What are the most common food allergens associated with anaphylaxis? A: The most common food allergens that can cause anaphylaxis are cow s milk, eggs, wheat, soybeans, peanuts, tree nuts (walnuts, cashews, pistachios, pecans, etc.), fish and shellfish. 13 Q: Why is food intolerance often confused with food allergies? A: According to the NIAID food allergy guidelines, food allergies and food intolerance share some of the same symptoms; however, food intolerance does not involve the immune system. It can cause great discomfort but is not life-threatening. Some people with food intolerances are not able to digest certain foods because their bodies lack the specific enzyme needed to break down that food. 3 Q: Are some people at higher risk for food allergy-induced anaphylaxis than others? A: The highest-risk groups for anaphylaxis associated with food allergy include: Adolescents and young adults (because of inconsistent behaviors related to avoiding triggers and carrying epinephrine auto-injectors) 2 Individuals with known food allergy and a prior history of anaphylaxis 13 Individuals with asthma 13 Q: How much of a food allergen does it take to cause a reaction? A: Food allergens are not always obvious or easily identifiable. Even trace amounts of a food allergen can cause a reaction in someone who is allergic. 7 The allergen does not need to be ingested; in some cases, skin contact or inhalation can trigger a reaction. 28 Avoidance of allergic triggers is the critical first step to prevent a serious health emergency; however, accidental exposure may still happen. This is why it is important to be prepared with an anaphylaxis action plan, which includes avoiding known allergens, recognizing symptoms and having access to two epinephrine auto-injectors. 1,12,23 Carrying an epinephrine auto-injector does not prevent patients from having an anaphylactic reaction; hence, patients must avoid their allergen at all times. 3,6,14 If experiencing anaphylaxis, use an epinephrine auto-injector and seek immediate emergency medical attention. 3 Important Safety Information (cont d...) Tell your doctor if you have certain medical conditions such as asthma, depression, thyroid disease, Parkinson s disease, diabetes, high blood pressure and heart disease, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell your doctor all the medicines you take, especially medicines for asthma. 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 take the EpiPen or EpiPen Jr Auto Injector. Please see additional Important Safety Information on next page.

6 6 Q: What should people at risk for anaphylaxis look for in food labels? A: By law, the eight major allergens (cow s milk, eggs, wheat, soybeans, peanuts, tree nuts including walnuts, cashews, pistachios and pecans, fish and shellfish) must be noted on all packaged food labels in the U.S., either in the ingredient list or on a separate allergen statement. 29 However, individuals with food allergies should be aware that advisory or precautionary labeling (i.e., may contain, in a facility that also processes ) is not regulated and is solely voluntary. 29 Q: Other than food, what are the most common triggers that lead to anaphylaxis? A: Other common triggers of anaphylaxis are insect venom, latex, medications or exercise-induced. In about 20% of cases, no trigger is identified, known as idiopathic anaphylaxis. 30,31,32,33 About EpiPen (epinephrine) and EpiPen Jr (epinephrine) Auto-Injectors Q: What are the appropriate uses and product features of the EpiPen and EpiPen Jr Auto-Injectors? A: The EpiPen and EpiPen Jr Auto-Injectors are used for the emergency treatment of life-threatening allergic reactions, or anaphylaxis. 34 EpiPen Auto-Injector has been the most prescribed epinephrine auto-injector in the U.S. for more than 20 years. 35 EpiPen Auto-Injector is available in two dosage strengths: EpiPen Auto-Injector delivers 0.3 mg epinephrine injection and is intended for individuals who weigh 66 pounds. 34 EpiPen Jr Auto-Injector delivers 0.15 mg epinephrine injection and is intended for individuals who weigh pounds. 34 EpiPen and EpiPen Jr Auto-Injectors are exclusively sold as two-packs, by prescription only. 34,36 Q: What is included in an EpiPen 2-Pak and EpiPen Jr 2-Pak? A: Each EpiPen 2-Pak and EpiPen Jr 2-Pak contains two single auto-injectors, instructions for use, and a training device and instructions on how to use the training device to help patients become familiar with the administration technique. The training device contains no drug product or needle. 34,36 The decision to exclusively offer the EpiPen 2-Pak aligns with recent clinical food allergy guidelines for patients at risk for or who have experienced anaphylaxis to have immediate access to two doses of epinephrine. 3 Q: What does epinephrine do during an anaphylactic reaction? A: During anaphylaxis, epinephrine works to relieve life-threatening symptoms by constricting blood vessels to increase blood pressure, relaxing muscles in the lungs to improve breathing, stimulating the heart and reducing hives and swelling that may occur around the face and lips. 3 Important Safety Information (cont d...) The most common side effects may include increase in heart rate, stronger or irregular heartbeat, sweating, nausea and vomiting, difficulty breathing, paleness, dizziness, weakness or shakiness, headache, apprehension, nervousness or anxiety. These side effects usually go away quickly, especially if you rest. Talk to your health care professional to see if EpiPen or EpiPen Jr Auto-Injector is right for you. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA-1088.

7 7 Instructions for Use Carefully read these Instructions for Use before you need to use your EpiPen or EpiPen Jr Auto-Injector. Before you use your EpiPen or EpiPen Jr Auto-Injector, make sure your health care provider shows you the right way to use it. If you have any questions, ask your health care provider. EpiPen and EpiPen Jr Auto-Injectors The EpiPen Auto-Injector is generally intended for patients who weigh 66 pounds or more (30 kilograms or more). The EpiPen Jr Auto-Injector is generally intended for patients who weigh approximately 33 to 66 pounds (15 to 30 kilograms). 3-Step Easy To Follow Instructions: 1. Prepare the EpiPen or EpiPen Jr Auto-Injector For Injection 2. Administer the EpiPen or EpiPen Jr Auto-Injector 3. Finalize the Injection Process (See detailed instructions on the following page) Indications EpiPen (epinephrine) 0.3 mg and EpiPen Jr (epinephrine) 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. Important Safety Information EpiPen Auto-Injectors contain a single dose of epinephrine, which you inject into your outer thigh. DO NOT INJECT INTO YOUR VEIN, BUTTOCK, FINGERS, TOES, HANDS OR FEET. In case of accidental injection, please seek immediate medical treatment. Epinephrine should be used with caution if you have heart disease or are taking certain medicines that can cause heartrelated (cardiac) symptoms. Please see additional Important Safety Information on next page.

8 8 1. Prepare the EpiPen or EpiPen Jr Auto-Injector For Injection Remove the auto-injector from the clear carrier tube. Flip open the yellow cap of your EpiPen or the green cap of your EpiPen Jr Auto-Injector carrier tube. 2. Administer the EpiPen or EpiPen Jr Auto-Injector Hold the auto-injector with orange tip near the outer thigh. Swing and firmly push the orange tip against the outer thigh until it clicks. Keep the auto-injector firmly pushed against the thigh at a 90 angle (perpendicular) to the thigh. Tip and slide the auto-injector out of the carrier tube. Hold firmly against the thigh for approximately 10 seconds to deliver the drug. The injection is now complete. 3. Finalize the Injection Process Grasp the auto-injector in your fist with the orange tip pointing downward. With your other hand, remove the blue safety release by pulling straight up without bending or twisting it. Remove the auto-injector from the thigh. The orange tip will extend to cover the needle. Note: The needle comes out of the orange tip. Never put your thumb, fingers or hand over the orange tip. Massage the injection area for 10 seconds. Get emergency medical help right away. You may need further medical attention. You may need a second EpiPen or EpiPen Jr Auto-Injector should symptoms persist or recur. Important Safety Information (cont d...) Tell your doctor if you have certain medical conditions such as asthma, depression, thyroid disease, Parkinson s disease, diabetes, high blood pressure and heart disease, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell your doctor all the medicines you take, especially medicines for asthma. 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 take the EpiPen or EpiPen Jr Auto Injector. Please see additional Important Safety Information on next page.

9 9 Important Information: Your auto-injector is designed to work through clothing. The blue safety release on the EpiPen and EpiPen Jr Auto-Injector helps to prevent accidental injection of the device. Keep the blue safety release on until you need to use it. Only inject into outer thigh. 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 medical help right away. Do not place patient information or any other foreign objects in carrier with auto-injector, as this may prevent you from removing the auto-injector for use. Q: Does the EpiPen Auto-Injector come with instructions? A: Yes, patient directions for use which includes illustrations are enclosed in each 2-Pak. In addition, directions on how to administer an EpiPen Auto-Injector are printed on the side of the auto-injector itself. In addition, each EpiPen 2-Pak and EpiPen Jr 2-Pak contains two single auto-injectors and a training device to help patients become familiar with the administration technique. 36 The training device has a gray color and contains no drug product or needle. 34 Patients should ask their health care professional to demonstrate how to use an EpiPen Auto-Injector. If a patient can t administer it, have the health care professional show a friend or relative. 36 Q: Can the EpiPen Auto-Injector be reused? A: No, although liquid remains in an EpiPen Auto-Injector following an injection, it cannot be reused. A patient should take used EpiPen or EpiPen Jr Auto-Injectors to the emergency room or health care professional s office for proper disposal. 34 Q: Do the EpiPen and EpiPen Jr Auto-Injectors expire? If so, what should a patient do when it expires? A: Like any medication, the EpiPen Auto-Injector has an expiration date, which is printed on the side of the Auto-Injector and end side of the carton. The effectiveness of this drug may decrease after the expiration date; therefore, care should be taken to refill the prescription before the expiration date. Individuals can register at MyEpiPen.com to receive expiration reminders. 34 Q: Where s the best place to keep the EpiPen Auto-Injector? A: The EpiPen Auto-Injector is transportable, but it should be kept at room temperature (25 C, 77 F) until the marked expiration date, when it should be replaced. The effectiveness of this drug may decrease after the expiration date. Therefore, care should be taken to refill the prescription before the expiration date. The EpiPen Auto-Injector should be protected from light and never refrigerated or kept where it might be exposed to extreme temperatures, such as in the glove compartment of a car. 34 Q: Is the EpiPen Auto-Injector carrier tube waterproof? A: No, the EpiPen Auto-Injector carrier tube has no rubber seal, so it is not waterproof. Important Safety Information (cont d...) The most common side effects may include increase in heart rate, stronger or irregular heartbeat, sweating, nausea and vomiting, difficulty breathing, paleness, dizziness, weakness or shakiness, headache, apprehension, nervousness or anxiety. These side effects usually go away quickly, especially if you rest. Talk to your health care professional to see if EpiPen or EpiPen Jr Auto-Injector is right for you. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA-1088.

10 10 Q: What signs and symptoms prompt the use of an EpiPen Auto-Injector? A: Signs and symptoms of anaphylaxis that may prompt the use of an EpiPen Auto-injector include hives or redness of the skin, tightness in the throat, breathing problems and/or a decrease in blood pressure. These may occur in any two body systems: central nervous system, skin, airway, cardiovascular system or gastrointestinal system. 1,2,5 Q: Who should receive a prescription for an EpiPen 2-Pak or EpiPen Jr 2-Pak? A: EpiPen 0.3 mg and EpiPen Jr 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self-administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. 36 Q: How many EpiPen Auto-Injectors have been dispensed in the U.S.? A: Since 1990, over 41 million EpiPen Auto-Injectors have been dispensed in the U.S. 35 Q: When did EpiPen Auto-Injector receive approval by the U.S. Food and Drug Administration? A: The EpiPen Auto-Injector was approved by the U.S. Food and Drug Administration on Dec. 22, It has been the #1 prescribed epinephrine auto-injector for more than 20 years. 35 Q: Should all EpiPen Auto-Injector patients have their own anaphylaxis action plan? A: Yes, EpiPen Auto-Injector patients should work with their health care professional to create an anaphylaxis action plan, which includes avoiding known allergens, recognizing symptoms and having access to two epinephrine auto-injectors. 1,12,23 EpiPen Auto-Injector is not a substitute for emergency medical treatment. Patients should seek emergency medical attention immediately following administration. These plans may be personalized to each patient to include their allergic triggers, other medical conditions, other medications they re currently taking, the specific dose of epinephrine prescribed to them and contact information for caregivers or family members. 37 Q: What happens if someone who has not been experiencing anaphylaxis is mistakenly injected with an EpiPen Auto-Injector? A: Epinephrine is a naturally-occurring hormone, also known as adrenaline. 2,38 Common side effects of epinephrine include faster, irregular or pounding heartbeat; sweating; nausea and vomiting; breathing problems; paleness; dizziness; weakness or shakiness; headache; and feelings of over excitement, nervousness or anxiety. 34 If an accidental injection happens, get medical help right away. Indications EpiPen (epinephrine) 0.3 mg and EpiPen Jr (epinephrine) 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. Important Safety Information EpiPen Auto-Injectors contain a single dose of epinephrine, which you inject into your outer thigh. DO NOT INJECT INTO YOUR VEIN, BUTTOCK, FINGERS, TOES, HANDS OR FEET. In case of accidental injection, please seek immediate medical treatment. Epinephrine should be used with caution if you have heart disease or are taking certain medicines that can cause heart-related (cardiac) symptoms. Please see additional Important Safety Information on next page.

11 11 Q: At what age can a child self-administer the EpiPen Auto-Injector? A: Parents should speak with their child s health care professional to determine what is appropriate for each child. Q: Where should a child keep an EpiPen Auto-Injector while at school? A: Children and their appropriate school personnel should have immediate access to his/her EpiPen Auto-Injector at all times, and should discuss school regulations for carrying epinephrine auto-injectors, as they may vary. School personnel should be informed of a child s history of anaphylaxis and the specific trigger(s) affecting the child. 3 Q: How should EpiPen Auto-Injector be properly mentioned in a news article? A: It s important to remember that although well-known, EpiPen Auto-Injector is a brand name, not a generic, and should only be used in connection with Mylan s epinephrine auto-injector devices. When writing EpiPen Auto-Injector, the first mention in all cases should include a registered trademark. Options are as follows: EpiPen Auto-Injector, EpiPen Jr Auto-Injector, EpiPen 2-Pak, EpiPen Jr 2-Pak and exclusively to its wholly-owned subsidiary, Mylan Specialty L.P. Q: Does Mylan Specialty offer an online resource for patients? A: Mylan Specialty s website, EpiPen.com, offers an online resource center with helpful information about anaphylaxis and EpiPen Auto-Injector. Patients can register on MyEpiPen.com to receive expiration reminders that prompt them to renew or refill their prescriptions before they expire. 34 Q: Does Mylan Specialty have a patient assistance program? A: Mylan Specialty has a patient assistance program available for qualifying patients. Patients can find out if they are eligible for the program by ing info@rxassist.org or calling the customer service line to speak with a representative at Q: Is there a customer service line? A: If a person has questions, they can call the customer service line to speak with a representative at Important Safety Information (cont d...) Tell your doctor if you have certain medical conditions such as asthma, depression, thyroid disease, Parkinson s disease, diabetes, high blood pressure and heart disease, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell your doctor all the medicines you take, especially medicines for asthma. 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 take the EpiPen or EpiPen Jr Auto Injector. The most common side effects may include increase in heart rate, stronger or irregular heartbeat, sweating, nausea and vomiting, difficulty breathing, paleness, dizziness, weakness or shakiness, headache, apprehension, nervousness or anxiety. These side effects usually go away quickly, especially if you rest. Talk to your health care professional to see if EpiPen or EpiPen Jr Auto-Injector is right for you You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA-1088.

12 12 Indications EpiPen (epinephrine) 0.3 mg and EpiPen Jr (epinephrine) 0.15 mg Auto-Injectors are for the emergency treatment of life-threatening allergic reactions (anaphylaxis) caused by allergens, exercise, or unknown triggers; and for people who are at increased risk for these reactions. EpiPen and EpiPen Jr are intended for immediate self administration as emergency supportive therapy only. Seek immediate emergency medical treatment after use. Important Safety Information EpiPen Auto-Injectors contain a single dose of epinephrine, which you inject into your outer thigh. DO NOT INJECT INTO YOUR VEIN, BUTTOCK, FINGERS, TOES, HANDS OR FEET. In case of accidental injection, please seek immediate medical treatment. Epinephrine should be used with caution if you have heart disease or are taking certain medicines that can cause heart-related (cardiac) symptoms. Tell your doctor if you have certain medical conditions such as asthma, depression, thyroid disease, Parkinson s disease, diabetes, high blood pressure and heart disease, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell your doctor all the medicines you take, especially medicines for asthma. 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 take the EpiPen or EpiPen Jr Auto Injector. The most common side effects may include increase in heart rate, stronger or irregular heartbeat, sweating, nausea and vomiting, difficulty breathing, paleness, dizziness, weakness or shakiness, headache, apprehension, nervousness or anxiety. These side effects usually go away quickly, especially if you rest. Talk to your health care professional to see if EpiPen or EpiPen Jr Auto-Injector is right for you. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA References: 1. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report Second National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2): Simons FER. Anaphylaxis. J Allergy Clin Immunol. 2010;125(suppl 2):S161-S Boyce JA, Assa ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(6):S1-S Sicherer SH, Mahr T; American Academy of Pediatrics Section on Allergy and Immunology. Management of food allergy in the school setting. Pediatrics. 2010;126(6): Ben-Shoshan M, Clarke AE. Anaphylaxis: Past, present and future. Allergy. 2010;66(1): Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Allergy Clin Immunol. 2010;126(3): e1-e Sampson H, et al. Food anaphylaxis. British Medical Bulletin. 2000;56 (No. 4): Neugut Al, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch of Intern Med. 2001;161(1): Clark S, Espinola J, et al. Frequency of U.S. emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol. 2011;127(3): Vander Leek TK, Liu AH, Stefanski K, Blacker B, Bock SA. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J Pediatr. 2000;137(6): Hourihane JO, Kilburn SA, Dean P. Clinical characteristics of peanut allergy. Clin Exp Allergy. 1997;27(6): Simons FER. Anaphylaxis: Recent advances in assessment and treatment. J Allergy Clin Immunol. 2009;124(4): Munoz-Furlong A, Weiss C, et al. Characteristics of food-allergic patients placing them at risk for a fatal anaphylactic episode. Anaphylaxis and Drug Allergy. 2009;9(1): Burks AW, et al. ICON: Food Allergy. J Allergy Clin Immunol. 2012;129(4): Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to food. J Allergy Clin Immunol. 2001;107(1): Bock SA. Further fatalities caused by anaphylactic reactions to food, [letter]. J Allergy Clin Immunol. 2007;119(4): Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Eng J Med. 1992;327(6): Lieberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol. 2005;95(3): Simons FER. Anaphylaxis in the community: learning from the survivors. J Allergy Clin Immunol. 2009;124(2): Liu AH, Jaramillo R, et al. National prevalence and risk factors for food allergy and relationship to asthma: Results from the National Health and Nutrition Examination Survey J Allergy Clin Immunol. 2010;126(4): Gupta R, Springston E, et al. The prevelance, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128(1):e9-e Chapman J, Bernstein L, et al. Food allergy: a practice parameter. Ann Allergy Asthma Immunol. 2006;3(96):S1-S Sicherer SH, Simons FER. Quandaries in prescribing an emergency action plan and selfinjectable epinephrine for first-aid management of anaphylaxis in the community. J Allergy Clin Immunol. 2005;115(3): Branum A, Lukas S. Food allergy among U.S. children: Trends in prevalence and hospitalizations. National Center for Health Statistics data brief. 2008: Sicherer SH, Munoz-Furlong A, et al. U.S. prevalence of self-reported peanut, tree nut and sesame allergy: 11 year follow-up. J Allergy Clin Immunol. 2010;125(6): McIntyre C, Sheetz A, et al. Administration of epinephrine for life-threatening allergic reactions in school settings. Pediatrics. 2005;116(5): Pumphrey RSH. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30(8): Simonte SJ, Sonhui M, Shideh M, Sicherer S. Relevance of casual contact with peanut butter in children with peanut allergy. J Allergy Clin Immunol. 2003;112(1): U.S. Food and Drug Administration. Food allergen labeling and consumer protection act of 2004 (public law , title II) Decker WW, Campbell RL, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008;122(6): Lieberman P, Kemp S, et al. The diagnosis and management of anaphylaxis: An updated practice parameter. J Allergy Clin Immunol. 2005;116(5): Jarvinen-Seppo K, Feldweg A, et al. 2008: Exercise-induced anaphylaxis and food-dependent exercise-induced anaphylaxis. Seminar presented at: The American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting; 2012 Mar 3 7; Orlando, Florida. 33. Yocum MW. Assessment of patients who have experienced anaphylaxis: a 3-year survey. Mayo Clin Proc EpiPen [patient insert]. Napa, CA: Mylan Specialty, L.P.; SDI Health, Physician Disease & Diagnosis Audit, Drug Uses for DX Code Anaphylactic Shock, EpiPen [package insert], Napa, CA: Mylan Specialty, L.P.; Sicherer SH, Simons FER. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics. 2007;119(3); Simons K, et al. Epinephrine and its use in anaphylaxis: current issues. Curr Opin Allergy Clin Immunol. 2010;10(4):

13 PRESCRIBING INFORMATION DESCRIPTION Each EpiPen Auto-Injector delivers a single dose of 0.3 mg epinephrine injection, USP, 1:1000 (0.3 ml) in a sterile solution. Each EpiPen Jr Auto-Injector delivers a single dose of 0.15 mg epinephrine injection, USP, 1:2000 (0.3 ml) in a sterile solution. The EpiPen Auto-Injector and EpiPen Jr Auto- Injector (henceforth referred to as EpiPen and EpiPen Jr Auto-Injector) each contain 2 ml epinephrine solution. Approximately 1.7 ml remains in the auto-injector after activation and cannot be used. Each 0.3 ml in the EpiPen Auto-Injector contains 0.3 mg epinephrine, 1.8 mg sodium chloride, 0.5 mg sodium metabisulfite, hydrochloric acid to adjust ph, and Water for Injection. The ph range is Each 0.3 ml in the EpiPen Jr Auto-Injector contains 0.15 mg epinephrine, 1.8 mg sodium chloride, 0.5 mg sodium metabisulfite, hydrochloric acid to adjust ph, and Water for Injection. The ph range is Epinephrine is a sympathomimetic catecholamine. Chemically, epinephrine is B-(3, 4-dihydroxyphenyl)-a-methylaminoethanol, 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 EpiPen and EpiPen Jr Auto-Injectors if the epinephrine solution appears discolored. EpiPen and EpiPen Jr Auto-Injectors do not contain latex. CLINICAL PHARMACOLOGY Epinephrine is the drug of choice for the emergency treatment of severe allergic reactions (Type I) to insect stings or bites, foods, drugs, and other allergens. It can also be used in the treatment of anaphylaxis of unknown cause (idiopathic anaphylaxis) or exercise-induced anaphylaxis. When given intramuscularly or subcutaneously it has a rapid onset and short duration 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 that helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may be effective in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder. INDICATIONS AND USAGE EpiPen and EpiPen Jr Auto-Injectors 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, mosquitos), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exerciseinduced anaphylaxis. EpiPen and EpiPen Jr Auto-Injectors 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. Selection of the appropriate dosage strength is determined according to patient body weight (see DOSAGE AND ADMINISTRATION section). Such 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. EpiPen and EpiPen Jr Auto-Injectors are intended for immediate self-administration as emergency supportive therapy only and are not a substitute for immediate medical care. CONTRAINDICATIONS There are no absolute contraindications to the use of epinephrine in a life-threatening situation. WARNINGS EpiPen and EpiPen Jr Auto-Injectors should only be injected into the anterolateral aspect of the thigh. 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. 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. Treatment should be directed at vasodilation in addition to further treatment of anaphylaxis (see ADVERSE REACTIONS). 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. 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. 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 lifethreatening 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 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 should be administered with caution in 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, e.g., digitalis, diuretics, or anti-arrhythmics, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. It should be recognized that the presence of these conditions is not a contraindication to epinephrine administration in an acute, lifethreatening situation. Epinephrine is light sensitive and should be stored in the carrier tube provided. Store at 20 to 25 C (68 to 77 F); excursions permitted to 15 C-30 C (59 F-86 F) (See USP Controlled Room Temperature). Do not refrigerate. Protect from light. Before using, check to make sure the solution in the auto-injector is not discolored. Replace the auto-injector if the solution is discolored or contains a precipitate. PRECAUTIONS (1) General EpiPen and EpiPen Jr Auto-Injectors 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. Epinephrine is essential for the treatment of anaphylaxis. Patients 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. It must be clearly determined that the patient is at risk of future anaphylaxis, since the following risks may be associated with epinephrine administration (see DOSAGE and ADMINISTRATION). Epinephrine should be used with caution in patients who have cardiac arrhythmias, coronary artery or organic heart disease, hypertension, or in patients who are on drugs that may sensitize the heart to arrhythmias, e.g., digitalis, diuretics, quinidine, or other anti-arrhythmics. In such patients, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. The effects of epinephrine may be potentiated by tricyclic antidepressants and monoamine oxidase inhibitors. Some patients may be at greater risk of developing adverse reactions after epinephrine administration. These include: hyperthyroid individuals, individuals with cardiovascular disease, hypertension, or diabetes, elderly individuals, pregnant women, pediatric patients under 30 kg (66 lbs.) body weight using EpiPen Auto-Injector, and pediatric patients under 15 kg (33 lbs.) body weight using EpiPen Jr Auto-Injector. Despite these concerns, epinephrine is essential for the treatment of anaphylaxis. Therefore, patients with these conditions, and/or any other person who might be in a position to administer EpiPen or EpiPen Jr Auto-Injector to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which epinephrine should be used. (2) Information for Patients Complete patient information, including dosage, direction for proper administration and precautions can be found inside each EpiPen/EpiPen Jr Auto-Injector carton. (Continued on back)