Anaphylaxis and epinephrine: what the guidelines and labels say

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1. World allergy organization anaphylaxis guidance 2020. Cardona V, World Allergy Organ J, 2020. E2Good GuidelinePMID 33204386; DOI 10.1016/j.waojou.2020.100472; cited 798 times, relative citation ratio 57.75 (NIH iCite, 2026-10-16)
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   Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions.

   Intramuscular epinephrine (adrenaline) continues to be the first-line treatment for anaphylaxis. Nevertheless, its use remains suboptimal.

   After an anaphylaxis occurrence, patients should be referred to a specialist to assess the potential cause and to be educated on prevention of recurrences and self-management.

2. EAACI guidelines: Anaphylaxis (2021 update). Muraro A, Allergy, 2022. E2Good GuidelinePMID 34343358; DOI 10.1111/all.15032; cited 415 times, relative citation ratio 48.27 (NIH iCite, 2026-10-16)
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   The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community.

   The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase.

   Structured, comprehensive training for people at risk of anaphylaxis is recommended.

3. International consensus on (ICON) anaphylaxis. Simons FE, World Allergy Organ J, 2014. E2Good Consensus statementPMID 24920969; DOI 10.1186/1939-4551-7-9; cited 272 times, relative citation ratio 12.68 (NIH iCite, 2026-10-16)
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   They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation.

   Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice.

   These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction.

   For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences.

4. Zyrtec Hives (cetirizine HCl 10 mg tablets), OTC Drug Facts. Kenvue Brands LLC, 2025. Official text FDA label
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   Not a Substitute for Epinephrine. If your doctor has prescribed an epinephrine injector for "anaphylaxis" or severe allergy symptoms that could occur with your hives, never use this product as a substitute for the epinephrine injector.

   These symptoms may be signs of anaphylactic shock. This condition can be life threatening if not treated by a health professional immediately. Symptoms of anaphylactic shock may occur when hives first appear or up to a few hours later.

5. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. Sampson HA, N Engl J Med, 1992. E2Good Observational studyPMID 1294076; DOI 10.1056/NEJM199208063270603; cited 1,160 times, relative citation ratio 45.32 (NIH iCite, 2026-10-16)
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   Dangerous anaphylactic reactions to food occur in children and adolescents. The failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome.

   The six patients who died had symptoms within 3 to 30 minutes of the ingestion of the allergen, but only two received epinephrine in the first hour. All the patients who survived had symptoms within 5 minutes of allergen ingestion, and all but one received epinephrine within 30 minutes.

   All had known food allergies, but had unknowingly ingested the foods responsible for the reactions.

6. Lessons for management of anaphylaxis from a study of fatal reactions. Pumphrey RS, Clin Exp Allergy, 2000. E2Good Observational studyPMID 10931122; DOI 10.1046/j.1365-2222.2000.00864.x; cited 718 times, relative citation ratio 24.44 (NIH iCite, 2026-10-16)
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   Adrenaline (epinephrine) was used in treatment of 62% of fatal reactions but before arrest in only 14%.

   Immediate recognition of anaphylaxis, early use of adrenaline, inhaled beta agonists and other measures are crucial for successful treatment.

   All fatal reactions thought to have been due to food caused difficulty breathing that in 86% led to respiratory arrest; shock was more common in iatrogenic and venom reactions. The median time to respiratory or cardiac arrest was 30 min for foods, 15 min for venom and 5 min for iatrogenic reactions.

7. Clinical features of acute allergic reactions to peanut and tree nuts in children. Sicherer SH, Pediatrics, 1998. E2Good Observational studyPMID 9651458; DOI 10.1542/peds.102.1.e6; cited 341 times, relative citation ratio 9.48 (NIH iCite, 2026-10-16)
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   Eighty-nine percent of the reactions involved the skin (urticaria, angioedema), 52% the respiratory tract (wheezing, throat tightness, repetitive coughing, dyspnea), and 32% the gastrointestinal tract (vomiting, diarrhea).

8. Anaphylaxis: A 2023 practice parameter update. Golden DBK, Ann Allergy Asthma Immunol, 2024. E2Good Practice parameterPMID 38108678; DOI 10.1016/j.anai.2023.09.015; cited 282 times, relative citation ratio 80.34 (NIH iCite, 2026-10-16)
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   In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure.

   Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders.

   If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response.

   Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911.

9. EpiPen and EpiPen Jr (epinephrine injection) auto-injector, Prescribing Information. Viatris Specialty LLC, 2023. Official text FDA label
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   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 acts on both alpha- and beta-adrenergic receptors.

   EpiPen and EpiPen Jr 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, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis.

   Inject the single-dose EpiPen or EpiPen Jr intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject intravenously, and do not inject into buttocks, into digits, hands or feet [see Warnings and Precautions (5.2)].

   With severe persistent anaphylaxis, repeat injections with an additional EpiPen or EpiPen Jr may be necessary. More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Warnings and Precautions (5.1)].

   Patients greater than or equal to 30 kg (approximately 66 pounds or more): EpiPen 0.3 mg

   Patients 15 kg to 30 kg (33 pounds to 66 pounds): EpiPen Jr 0.15 mg

10. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. Shaker MS, J Allergy Clin Immunol, 2020. E2Good Practice parameterPMID 32001253; DOI 10.1016/j.jaci.2020.01.017; cited 524 times, relative citation ratio 37.48 (NIH iCite, 2026-10-16)
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    Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved.

    Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis.

    Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy.

11. Fatalities due to anaphylactic reactions to foods. Bock SA, J Allergy Clin Immunol, 2001. E2Good Observational studyPMID 11150011; DOI 10.1067/mai.2001.112031; cited 1,114 times, relative citation ratio 32.94 (NIH iCite, 2026-10-16)
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    In those subjects for whom data were available, all but 1 was known to have asthma, and most of these individuals did not have epinephrine available at the time of their fatal reaction.

    In this series, peanuts and tree nuts accounted for more than 90% of the fatalities.

    The sexes were equally affected; most victims were adolescents or young adults, and all but 1 subject were known to have food allergy before the fatal event.

12. Fatal Anaphylaxis: Mortality Rate and Risk Factors. Turner PJ, J Allergy Clin Immunol Pract, 2017. Review Expert reviewPMID 28888247; DOI 10.1016/j.jaip.2017.06.031; cited 400 times, relative citation ratio 19.75 (NIH iCite, 2026-10-16)
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    Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk.

    Upright posture is a feature of fatal anaphylaxis to both food and venom.

    Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis.

13. Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis. Umasunthar T, Clin Exp Allergy, 2013. E1Strong Meta-analysisPMID 24118190; DOI 10.1111/cea.12211; cited 189 times, relative citation ratio 7.94 (NIH iCite, 2026-10-16)
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    In food-allergic people, fatal food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI 0.94, 3.45; range 0.63, 6.68).

    Fatal food anaphylaxis for a food-allergic person is rarer than accidental death in the general population.

    At age 0-19, the incidence rate is 3.25 (1.73, 6.10; range 0.94, 15.75; sensitivity analysis 1.18-6.13).

14. H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review. Sheikh A, Allergy, 2007. E1Strong Systematic reviewPMID 17620060; DOI 10.1111/j.1398-9995.2007.01435.x; cited 139 times, relative citation ratio 4.67 (NIH iCite, 2026-10-16)
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    We found no studies that satisfied the inclusion criteria.

    Based on this review, we are unable to make any recommendations for clinical practice.

    H(1)-antihistamines are commonly used as an adjuvant therapy in the treatment of anaphylaxis.

15. AUVI-Q (epinephrine injection) auto-injector 0.3 mg, 0.15 mg, 0.1 mg, Prescribing Information. Kaleo, Inc., 2025. Official text FDA label
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    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.

    It is recommended that patients are prescribed and have immediate access to two AUVI-Q devices at all times.

    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.

    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

    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 [see Warnings and Precautions (5.1)].

16. neffy (epinephrine nasal spray) 2 mg and 1 mg, Prescribing Information. ARS Pharmaceuticals Operations, Inc., 2026. Official text FDA label
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    Neffy is indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients who weigh 15 kg or greater.

    If neffy is frozen and is needed in an emergency, do not wait to thaw, seek emergency medical care immediately [see How Supplied/Storage and Handling (16)].

    In the absence of clinical improvement or if symptoms worsen after the initial treatment, a second dose of neffy may be administered in the same nostril with a second nasal spray starting 5 minutes after the first dose.

    30 kg or Greater | One spray of neffy 2 mg 15 kg to less than 30 kg | One spray of neffy 1 mg

17. Epinephrine Injection, USP auto-injector 0.3 mg and 0.15 mg, Prescribing Information. Amneal Pharmaceuticals of New York LLC, 2026. Official text FDA label
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    30 kg or greater | 0.3 mg 15 kg to less than 30 kg | 0.15 mg

    Since the doses of epinephrine delivered from Epinephrine Injection are fixed, use other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.

    Epinephrine Injection is indicated for the emergency treatment of type I allergic reactions, including anaphylaxis in adult and pediatric patients who weigh 15 kg or greater.

18. About the role and underlying mechanisms of cofactors in anaphylaxis. Wölbing F, Allergy, 2013. Review Expert reviewPMID 23909934; DOI 10.1111/all.12193; cited 123 times, relative citation ratio 4.85 (NIH iCite, 2026-10-16)
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    A number of conditions were identified that modulate the onset of anaphylaxis such as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis.

    Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as 'wheat-dependent exercise-induced anaphylaxis' (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor.