Updates in Epinephrine Guidelines

Authors

  • Susan Waserman, MSc, MDCM, FRCPC Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Canada
  • Heather Cruickshank, BA Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Canada

DOI:

https://doi.org/10.58931/cait.2025.5178

Abstract

Epinephrine is the first line treatment for anaphylaxis, which is a serious allergic reaction that can rapidly progress and may cause death. As a nonselective adrenergic agonist, epinephrine rapidly works to increase vasoconstriction and peripheral vascular resistance, increase cardiac output, reverse bronchoconstriction and mucosal edema, and inhibit the release of mediators of inflammation from mast cells and basophils. The anaphylaxis guidelines developed by the Joint Task Force on Practice Parameters (JTFPP) in 2020, the World Allergy Organization (WAO) in 2020, and the European Academy of Allergy and Clinical Immunology (EAACI) in 2021 advise clinicians to prescribe self-injectable epinephrine to individuals at risk of anaphylaxis and educate them on when and how to administer it. In 2023, the JTFPP updated its anaphylaxis practice parameter to address seven key topic areas, including multiple questions and recommendations related to epinephrine prescription and use. The practice parameter authors graded each recommendation as conditional or strong, based in part on the certainty of the supporting evidence. We provide an overview of key recommendations and discuss their applications in the Canadian context.

It is important to note that in Canada, EpiPen® autoinjectors are currently the sole epinephrine delivery devices available with premeasured doses of epinephrine for the emergency treatment of allergic reactions. These autoinjectors should be administered intramuscularly into the anterolateral thigh. Additional epinephrine devices may become available in the future, including the first epinephrine nasal spray (neffy®). There is a wider variety of epinephrine devices available in the United States, including multiple brands of epinephrine autoinjectors (Adrenaclick®, Auvi-Q®, EpiPen®/EpiPen® Jr., and generic versions). Additionally, there is one brand of epinephrine prefilled syringe (Symjepi™) and one brand of nasal spray (neffy®). Although the anaphylaxis practice parameter update was published before the U.S. Food and Drug Administration had approved neffy®, we believe its recommendations for epinephrine prescription and use may be appropriately extended to include epinephrine nasal spray where it is available.

Author Biographies

Susan Waserman, MSc, MDCM, FRCPC, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Canada

Dr. Susan Waserman is a Professor of Medicine, Director of the Division of Clinical Immunology and Allergy at McMaster University and the Adverse Reactions Clinic at the Firestone Institute of Respiratory Health, St Joseph’s Healthcare, Hamilton. She is extensively involved in medical education in both academic and community settings, in addition to an active hospital‑based clinical practice in adult and pediatric Clinical Immunology and Allergy. Activities include practice guidelines in food allergy, allergic rhinitis, anaphylaxis, hereditary angioedema, and urticaria. Her research interests include mechanisms and treatment of peanut allergy. She is Director of the Schroeder Allergy and Immunology Research Institute, and holds the Schroeder Chair in Allergy and Immunology Research. She is President of the Canadian Allergy, Asthma, and Immunology Foundation and past President of the Canadian and Ontario Societies of Allergy and Clinical Immunology. She is also Chair of the Medical and Scientific Committee of Asthma Canada, medical advisor to Food Allergy Canada and on the Board of Directors of the Canadian Hereditary Angioedema Network and Asthma Canada.

Heather Cruickshank, BA, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Canada

Heather Cruickshank is a research coordinator, medical writer, and educational content developer. Her research interests include allergy management in the community and transition support for adolescents and young adults in healthcare and education. She has contributed to the development of practice guidelines and medical training materials related to allergy and anaphylaxis, education and support programs for youth with chronic conditions, and e-learning modules on a variety of professional development topics.

References

Dribin TE, Muraro A, Camargo CA Jr, Turner PJ, Wang J, Roberts G, et al. Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report-a GA2LEN project. J Allergy Clin Immunol. Forthcoming. Epub 2025 Jan 27.

Shaker MS, Wallace DV, Golden DBK, Oppenheimer J, Bernstein JA, Campbell RL, et al. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020 Apr;145(4):1082-1123.

Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World Allergy Organization anaphylaxis guidance 2020. World Allergy Org J. 2020 Oct;13(10):100472.

Muraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, et al. EAACI guidelines: Anaphylaxis (2021 update). Allergy. 2021;77(2):357-377.

Golden DBK, Wang J, Waserman S, Akin C, Campbell RL, Ellis AK, et al. Anaphylaxis: a 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124-176.

ARS Pharma. ARS Pharmaceuticals files for approval of neffy® in Canada and the United Kingdom on behalf of licensing partner ALK-Abelló A/S [Internet]. San Diego: ARS Pharma; 2025 Jan 6 [cited May 2025 May 7]. Available from https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-files-approval-neffyr-canada-and-united

Patel N, Chong KW, Yip AYG, Ierodiakonou D, Bartra J, Boyle RJ, et al. Use of multiple epinephrine doses in anaphylaxis: a systematic review and meta-analysis. 2021;148(5):1307-1315.

Dreborg S, Walter G, Kim H. International recommendations on epinephrine auto-injector doses often differ from standard weight-based guidance: a review and clinical proposals. Allergy Asthma Clin Immunol. 2022;18(1):102.

Li LDX, Abrams EM, Lavine E, Hildebrand K, Mack DP. CSACI position statement: transition recommendations on existing epinephrine autoinjectors. Allergy Asthma Clin Immunol. 2021;17(1):130.

Halbrich M, Mack DP, Carr S, Watson W, Kim H. (2015). CSACI position statement: Epinephrine auto-injectors and children <15 kg. Allergy Asthma Clin Immunol. 2015;11:20.

Kafal A, Burnette A, Chase N, Soteres D, Geng B, Kaplan H, et al. A survey of allergists, pediatricians, and primary care physicians about the utilization of epinephrine. J Allergy Clin Immunol. 2024;153(2 Suppl):AB76.

ARS Pharma. ARS Pharmaceuticals’ neffy® (epinephrine nasal spray) 1 mg is now available in the United States for type i allergic reactions, including anaphylaxis, in pediatric patients weighing 15 to < 30 kilograms [Internet]. San Diego: ARS Pharma; 2025 May 7 [cited 7 May 2025]. Available from https://www.globenewswire.com/news-release/2025/5/7/3076085/0/en/ARS-Pharmaceuticals-neffy-epinephrine-nasal-spray-1-mg-is-Now-Available-in-the-United-States-for-Type-I-Allergic-Reactions-including-Anaphylaxis-in-Pediatric-Patients-Weighing-15-t.html

Lowenthal R, Dorsey B, Burrell B. Comparative stability of three epinephrine products under extreme temperature conditions. J Allergy Clin Immunol. 2024;153(2 Suppl):AB371.

Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391-397.

Abrams EM, Ellis AK, Vander Leek T, Alqurashi W, Begin P, Chan ES, et al. Considerations for at-home management of food-induced anaphylaxis [Internet]. Ottawa: CSACI; 2023 Aug 14 [cited 7 May 2025]. Available from https://www.csaci.ca/considerations-for-at-home-management-of-food-induced-anaphylaxis/

Casale TB, Wang J, Oppenheimer J, Nowak-Wegrzyn A. Acute at-home management of anaphylaxis: 911: what is the emergency? J Allergy Clin Immunol Pract. 2022 Sept;10(9):2274–2279.

Prince BT, Mikhail I, Stukus DR. Underuse of epinephrine for the treatment of anaphylaxis: missed opportunities. J Asthma Allergy. 2018;11:143–151.

Miles LM, Ratnarajah K, Gabrielli S, Abrams EM, Protudjer JLP, Bégin P, et al. Community use of epinephrine for the treatment of anaphylaxis: A review and meta-analysis. J Allergy Clin Immumol Pract. 2021 June;9(6):2321–2333.

Cardona V, Ferré-Ybarz L, Guilarte M, Moreno-Pérez N, Gómez-Galán C, Alcoceba-Borràs E, et al. Safety of adrenaline use in anaphylaxis: a multicentre register. Int Arch Allergy Immunol. 2017;173(3):171–177.

Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, Hess EP. Epinephrine in anaphylaxis: higher risk of cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular epinephrine. J Allergy Clin Immunol Pract. 2015;3:76-80.

Waserman S, Cruickshank H, Hildebrand KJ, Mack D, Bantock L, Bingemann T, et al. Prevention and management of allergic reactions to food in child care centers and schools: Practice guidelines. J Allergy Clin Immunol. 2021 May;147(5):1561-1578.

Waserman S, Avilla E, Harada L, Allen M, Isaranuwatchai W, Perdrizet J, Kastner M. To stock or not to stock? Implementation of epinephrine autoinjectors in food establishments. J Allergy Clin Immunol Pract. 2019 Feb;7(2):678–680.e5.

Downloads

Published

2025-06-02

How to Cite

1.
Waserman S, Cruickshank H. Updates in Epinephrine Guidelines. Can Allergy Immunol Today [Internet]. 2025 Jun. 2 [cited 2025 Jun. 7];5(1):11–17. Available from: https://canadianallergyandimmunologytoday.com/article/view/5-1-Waserman_et_al

Issue

Section

Articles