What is the role of antihistamines (anti-histamine) in the treatment of anaphylaxis?

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From the Guidelines

Antihistamines are not first-line treatments for anaphylaxis but can be used as adjunctive therapy after epinephrine administration. In anaphylaxis, epinephrine (0.3-0.5 mg IM for adults, 0.15 mg for children <30 kg) should always be given first, followed by second-line agents including H1 antihistamines such as diphenhydramine (25-50 mg IV/IM for adults) or cetirizine (10 mg oral for adults) 1. H2 blockers like ranitidine (50 mg IV for adults) may also be added. Antihistamines help relieve cutaneous symptoms like urticaria and pruritus but do not treat the life-threatening respiratory and cardiovascular effects of anaphylaxis. They work by blocking histamine receptors, preventing histamine from binding and causing symptoms, but they cannot reverse the multiple inflammatory mediators involved in anaphylaxis.

Key Points

  • Antihistamines should never delay epinephrine administration in suspected anaphylaxis 1
  • The use of antihistamines may be associated with side effects that could confound assessment of anaphylaxis, such as altered level of consciousness with first-generation antihistamines 1
  • Patients should be monitored closely after antihistamine administration as part of comprehensive anaphylaxis management, which includes oxygen, IV fluids, and possibly corticosteroids 1
  • The certainty of evidence for the use of antihistamines in preventing biphasic anaphylaxis is very low, and additional well-designed controlled trials are needed to further inform this practice 1

Treatment Approach

The treatment approach for anaphylaxis should prioritize epinephrine administration, followed by adjunctive therapy with antihistamines and other agents as needed. The primary goal is to prevent morbidity and mortality, and to improve quality of life for patients with anaphylaxis. The use of antihistamines should be guided by the latest evidence and clinical guidelines, and patients should be closely monitored for potential side effects and interactions 1.

From the FDA Drug Label

INDICATIONS AND USAGE: ...For amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled...

The role of antihistamines, such as diphenhydramine, in the treatment of anaphylaxis is as an adjunct to epinephrine and other standard measures, used after the acute symptoms have been controlled. Key points include:

  • Antihistamines are not the primary treatment for anaphylaxis
  • Epinephrine is the primary treatment for anaphylaxis
  • Antihistamines are used to ameliorate allergic reactions after initial treatment with epinephrine 2

From the Research

Role of Antihistamines in Anaphylaxis Treatment

  • Antihistamines are considered second-line medications in the treatment of anaphylaxis, and should not be given in lieu of, or prior to, epinephrine 3.
  • Histamine H(1)-antagonists are valuable in mild anaphylactic reactions and can be given intravenously if possible 4.
  • Antihistamines, such as histamine H(1) and H(2) antagonists, can be considered as adjunct medications after epinephrine administration 5.
  • The use of antihistamines in anaphylaxis management has shown a beneficial effect, with patients treated with prehospital antihistamines being less likely to have uncontrolled reactions and to be admitted after the reaction 6.

Administration and Dosage

  • There is no specific dosage or administration guideline for antihistamines in anaphylaxis treatment mentioned in the provided studies.
  • However, it is recommended that antihistamines be given intravenously if possible, especially in mild anaphylactic reactions 4.

Importance of Epinephrine

  • Epinephrine remains the drug of choice for anaphylaxis treatment and should be administered intramuscularly as soon as the diagnosis is suspected 7, 3, 4, 5.
  • Delayed epinephrine administration is a risk factor for fatal anaphylaxis, and antihistamines should not delay the administration of epinephrine 6, 3, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anaphylaxis.

The Journal of emergency medicine, 2014

Research

Anaphylaxis: acute treatment and management.

Chemical immunology and allergy, 2010

Research

Anaphylaxis: Recognition and Management.

American family physician, 2020

Research

Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2023

Research

Adrenaline in the Acute Treatment of Anaphylaxis.

Deutsches Arzteblatt international, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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