Emergency Epinephrine Devices
modified September 2024
In addition to the well-known EpiPen, there are several other emergency epinephrine devices to treat anaphylaxis.1,2,7 Auvi-Q’s (US) 0.1 mg strength is marketed to have a lower risk of adverse effects (e.g., tremor, heart palpitations) in younger patients. It also has a smaller needle, designed to penetrate more often into muscle rather than bone in younger patients. Emerade (Canada) offers a 0.5 mg strength which is marketed as an option for heavier patients.8 However, data are lacking to support the benefits of these newer strengths over the well-used 0.15 mg and 0.3 mg strengths. Symjepi (US) is a prefilled syringe that is proposed to be more intuitive than an autoinjector since patients see the needle and depress the plunger themselves.37 Neffy (US) is a nasal spray which may be an option for some patients with a fear of needles. With high costs, shortages and recalls, generics, new strengths, and a prefilled syringe and nasal spray; there are lots of questions about the different formulations and which one a patient should use. The choice between devices is determined by insurance coverage, availability, and ease of use. This document answers frequently asked questions about emergency epinephrine devices.
Note: Anaphylaxis is a potentially life-threatening condition. No matter which device is prescribed, all patients should be instructed on the appropriate, immediate use of their product. They should also be instructed to seek immediate medical attention (i.e., call 911) after epinephrine administration. Patients should always have two emergency epinephrine devices available in case a second dose is required during an anaphylactic reaction.
Question |
Answer/Pertinent Information |
Which emergency epinephrine devices are available? |
Emergency epinephrine injection devices come in several strengths and are dispensed based on the patient’s weight:
EpiPen, EpiPen Jr: The auto-injector is packaged in a tube-like carrier about five and a half inches long.7
Adrenaclick (US) is a cylindrical device, similar in length and size to the EpiPen.7
Auvi-Q (US), Allerject (Canada): Credit card-sized (~3.5 x 2 inches) device with audio cues during administration.5,7 Symjepi (US) is a prefilled syringe, about four inches in length.29,37 Emerade (Canada) is an auto-injector, packaged in a tubular protective case, similar in size to the EpiPen.41
Neffy (US) is a 2 mg, one-dose nasal spray indicated for patients 30 kg and more.
|
Are there any alternatives to epinephrine injection devices? |
Epinephrine kits: Vials or ampules of epinephrine in a kit with two doses, needles, and syringes.
|
What are some of the new products on the horizon? |
Alternate modes of epinephrine administration (i.e., sublingual) are being studied:43
|
Are epinephrine injection devices interchangeable? |
US:
Canada:
One small pharmacokinetic study compared EpiPen to Auvi-Q in 69 healthy people. They demonstrated bioequivalence between these two products.12 |
What is the cost of each epinephrine device? |
Cost for packages of two devices:a
NOTE: Pricing between products varies based on discounts from individual pharmacies, insurance plans, and manufacturers. Reduced and $0 co-pay cards are available from most US manufacturers, for example (all information below is subject to change):
|
What is the role for training devices? |
Epinephrine devices are often used incorrectly, even by healthcare professionals.5,14,15
Patients must be trained on correct administration technique.5
A training device is included with each EpiPen and its generic product two pack.3,19 Additional trainers can be obtained by calling 800-395-3376. Adrenaclick and its generic product don’t come with a training device, but training devices are available. They can be ordered online at http://epinephrineautoinject.com/order-product-trainers/, by calling 855-EPINEPH, or by mailing the form found inside the device package.6 A training device is included with each Auvi-Q two pack. Additional trainers are available at www.auvi-q.com.16 Free training devices are available for Allerject (www.allerject.ca) and Emerade (www.emerade.ca). NOTE: Training devices are only available for epinephrine auto-injectors, not for the Symjepi prefilled syringe. Neffy (US) does not come with a training device, but training devices are available. They can be ordered online at https://www.neffypro.com/#sign-up.
|
How do epinephrine injection devices differ? |
Safety caps:
Epinephrine injection devices are recommended to be given into the outer thigh for fastest absorption.
|
How is emergency epinephrine nasal spray (Neffy) used? |
Epinephrine nasal spray (Neffy) is for single use, with the entire dose administered upon activation.46
|
What is the shelf life of epinephrine devices? |
The usual expiration date for epinephrine injection devices is 15 to 20 months from date of manufacture. Neffy nasal spray has a usual expiration of 30 months from date of manufacture and appears to be more stable to extreme heat exposure compared to EpiPen and Symjepi.45,47
Many of these devices expire before a patient needs to use them.
Encourage patients to store their epinephrine devices properly. One small pilot study of the injections suggests that epinephrine concentrations may be reduced by up to 14% when the devices are left in a car’s glovebox for 12 hours on a hot day.39 |
Are there risks associated with use of emergency epinephrine devices? |
There are no contraindications to the use of emergency epinephrine devices.20,29 Accidental self-injection with these devices is not uncommon.
There are reports of lacerations and embedded needles caused by epinephrine auto-injector use and misuse, mainly in children.1 Needle exposure once administration is complete:
There have been reports of the auto-injector labels sticking to the carrier tubes of the EpiPen, EpiPen Jr, and their authorized generics. This could cause a delay in the administration of the auto-injector. Pharmacists and patients should make sure auto-injectors can be easily removed from their outer tubes prior to dispensing and prior to when they need to use them, respectively.40 |
- Pricing is wholesale acquisition cost (WAC). US medication pricing by Elsevier, accessed January 2024 (September 2024 for Neffy).
Levels of Evidence
In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.
Level |
Definition |
Study Quality |
A |
Good-quality patient-oriented evidence.* |
|
B |
Inconsistent or limited-quality patient-oriented evidence.* |
|
C |
Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening. |
*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).
[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]
References
- Brown JC, Tuuri RE, Akhter S, et al. Lacerations and Embedded Needles Caused by Epinephrine Autoinjector Use in Children. Ann Emerg Med. 2016 Mar;67(3):307-315.e8.
- American Academy of Allergy, Asthma and Immunology. Allergic emergency medications. March 2020. https://www.aaaai.org/tools-for-the-public/drug-guide/allergic-emergency-medications. (Accessed January 4, 2024).
- Product information for EpiPen. Mylan Specialty L.P. Morgantown, WV 26505. February 2023.
- Lieberman JA, Oppenheimer J, Hernandez-Trujillo VP, Blaiss MS. Innovations in the treatment of anaphylaxis: A review of recent data. Ann Allergy Asthma Immunol. 2023 Aug;131(2):185-193.e10.
- Camargo CA Jr, Guana A, Wang S, Simons FE. Auvi-Q versus EpiPen: preferences of adults, caregivers, and children. J Allergy Clin Immunol Pract. 2013 May-Jun;1(3):266-72.e1-3.
- Product information for epinephrine injection, USP auto-injector. Amneal Pharmaceuticals of New York. Bridgewater, NJ 08807. February 2021.
- Consultants in Allergy & Asthma Care. Epinephrine choices in 2017; so many, and what to do? June 30, 2017. https://allergyasthmacare-doctor.com/epinephrine-choices-in-2017-so-many-and-what-to-do/#:~:text=Size%20of%20the%20Device%3A%20For,than%20%C2%BE%20inch%20wide%20and. (Accessed January 6, 2024).
- Bausch Health. Emerade. https://www.emerade.ca/. (Accessed January 6, 2024).
- FDA. Orange Book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/. (Accessed January 5, 2024).
- Academy of Managed Care Pharmacy. Proceedings of the AMCP integrated care summit: population health and quality improvement in anaphylaxis. J Manag Care Pharm 2014;20 (1 Suppl A):s1-9.
- Reisman M. Health Care Blog Watch: Pay-for-Delay and Authorized Generics Back in the Spotlight. P T. 2009 Dec;34(12):686-7.
- Edwards ES, Gunn R, Simons ER, et al.Bioavailability of epinephrine from Auvi-Q compared with EpiPen. Ann Allergy Asthma Immunol. 2013 Aug;111(2):132-7.
- Rachid O, Simons FE, Wein MB, et al.Epinephrine doses contained in outdated epinephrine auto-injectors collected in a Florida allergy practice. Ann Allergy Asthma Immunol. 2015 Apr;114(4):354-356.e1.
- Guerlain S, Hugine A, Wang L. A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference. Ann Allergy Asthma Immunol. 2010 Feb;104(2):172-7.
- Robinson MN, Dharmage SC, Tang ML. Comparison of adrenaline auto-injector devices: ease of use and ability to recall use. Pediatr Allergy Immunol. 2014 Aug;25(5):462-7.
- Product information for Auvi-Q. Kaleo. Richmond, VA 23219. November 2017.
- Guerlain S, Wang L, Hugine A. Intelliject's novel epinephrine autoinjector: sharps injury prevention validation and comparable analysis with EpiPen and Twinject. Ann Allergy Asthma Immunol. 2010 Dec;105(6):480-4.
- Pratt, E. Rising cost of EpiPens forcing some allergy sufferers to switch to syringes. Updated July 2017. http://www.huffingtonpost.com/healthline-/rising-cost-of-epipens-fo_b_11017710.html. (January 5, 2024).
- Product information for epinephrine injection, USP auto-injector. Mylan Specialty. Morgantown, WV 26505. February 2023.
- Song TT, Worm M, Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use. Allergy. 2014 Aug;69(8):983-91.
- Simons FE, Gu X, Simons KJ. Outdated EpiPen and EpiPen Jr autoinjectors: past their prime? J Allergy Clin Immunol. 2000 May;105(5):1025-30.
- Kerddonfak S, Manuyakorn W, Kamchaisatian W, et al. The stability and sterility of epinephrine prefilled syringe. Asian Pac J Allergy Immunol. 2010 Mar;28(1):53-7.
- Ashworth J, Trissel LA, Ashworth LD, (eds). Trissel’s Stability of Compounded Formulations. 6th ed. Washington, DC: American Pharmacists Association, 2018.
- Latimer AJ, Husain S, Nolan J, et al.Syringe Administration of Epinephrine by Emergency Medical Technicians for Anaphylaxis. Prehosp Emerg Care. 2018 May-Jun;22(3):319-325.
- Snapmedical. Products. https://snapmedicalindustries.com/. (Accessed January 5, 2024).
- FDA. FDA approves first generic version of EpiPen. August 16, 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm617173.htm. (Accessed January 5, 2024).
- Amneal Pharmaceuticals. Epinephrine injection, USP auto-injector. https://epinephrineautoinject.com/. (Accessed January 4, 2024).
- Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001 Nov;108(5):871-3.
- Product information for Symjepi. Adamis Pharmaceuticals. San Diego, CA 92130. February 2019.
- Product monograph for EpiPen. Mylan Specialty. Morgantown, WV 26505. April 2020.
- Product information for Adrenaclick. Amneal Pharmaceuticals. Bridgewater, NJ 08807. February 2021.
- Camilleri A.9 alternatives to Mylan’s EpiPen. October 2016. https://www.theodysseyonline.com/9-alternatives-mylans-epipen. (Accessed January 6, 2024).
- ARS Pharma. FDA issues complete response letter for neffy (epinephrine nasal spray) New Drug Application with request for additional study. September 19, 2023. https://ir.ars-pharma.com/news-releases/news-release-details/fda-issues-complete-response-letter-neffyr-epinephrine-nasal. (Accessed January 6, 2024).
- Pfizer/Mylan. Important update on EpiPen (epinephrine injection, USP) 0.3 mg auto-injectors from Pfizer and Mylan. June 5, 2019. https://www.fda.gov/media/127690/download. (Accessed January 6, 2024).
- Bausch Health, Canada. Emerade. https://www.emerade.ca/faq#recall. (Accessed January 25, 2024).
- Product monograph for Allerject. Valeo Pharma. Kirkland, QC H9H 4R9. December 2022.
- Preston J. Is Mylan’s EpiPen reign finally over? June 16, 2017. https://medcitynews.com/2017/06/mylans-epipen-reign-finally-over/. (Accessed January 6, 2024).
- Product information for epinephrine injection. Teva Pharmaceuticals USA. North Wales, PA 19454. January 2021.
- Lacwik P, Bialas AJ, Wielanek M, et al. Single, short-time exposure to heat inacar during sunny day can decrease epinephrine concentration in autoinjectors: a real-life pilot study. J Allergy Clin Immunol Pract. 2019 Apr;7(4):1362-1364.
- Pfizer/Mylan. Notice of precautionary handling instructions. November 1, 2018. https://www.fda.gov/media/117519/download. (Accessed January 6, 2024).
- Product monograph for Emerade. Bausch Health Canada. Laval, QC H7L 4A8. November 2022.
- Ferrandiz R. Adrenaline auto-injectors – longer needles needed to reach the muscle. March 17, 2016. https://www.emerade.com/hcp/articles/need-for-longer-aai-needles. (Accessed January 6, 2024).
- Lieberman JA, Oppenheimer J, Hernandez-Trujillo VP, Blaiss MS. Innovations in the treatment of anaphylaxis: A review of recent data. Ann Allergy Asthma Immunol. 2023 Aug;131(2):185-193.e10.
- Bausch Health, Canada. Emerade. https://www.emerade.ca/faq#recall. (Accessed January 25, 2024).
- Lowenthal R, Dorsey B, Burrell B. Comparative stability of three epinephrine products under extreme temperature conditions. J Allergy Clin Immunol 2024;153(2). Abstract only (AB371).
- Product information for Neffy. ARS Pharmaceuticals Operations. San Diego, CA 92130. August 2024.
- ARS harmaceuticals Operations. Neffy storage and handling. https://www.neffy.com/about/#storage-and-handling. (Accessed September 11, 2024).
Cite this document as follows: Clinical Resource, Emergency Epinephrine Injection Devices. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. January 2024. [400164]
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