What antihistamine (anti-histamine) is given in anaphylaxis (anaphylactic shock)?

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From the Guidelines

Diphenhydramine is the recommended antihistamine for anaphylaxis, administered at a dose of 25-50 mg intravenously or intramuscularly in adults (1-2 mg/kg in children, up to 50 mg maximum) after epinephrine has been given. The use of antihistamines in anaphylaxis is supported by the study 1, which emphasizes that antihistamines should not be administered before or in place of epinephrine. Epinephrine remains the first-line treatment for anaphylaxis due to its rapid onset of action and effectiveness in addressing life-threatening symptoms such as hypotension and respiratory distress.

Key Points to Consider:

  • Antihistamines are adjunctive therapy and should never delay or replace epinephrine administration 1.
  • Diphenhydramine helps manage symptoms like urticaria, pruritus, and angioedema by blocking H1 histamine receptors.
  • The dose of diphenhydramine recommended is 25-50 mg for adults and 1-2 mg/kg for children, up to a maximum of 50 mg, as stated in the study 1.
  • H2 blockers like ranitidine may be added in hospital settings, but there is limited evidence supporting their efficacy in anaphylaxis treatment 1.
  • Patients should be monitored closely for at least 4-6 hours after symptom resolution due to the risk of biphasic reactions.

Clinical Considerations:

The management of anaphylaxis prioritizes the administration of epinephrine due to its immediate effects on the body's response to the allergic reaction. Following epinephrine administration, antihistamines like diphenhydramine can be given to help alleviate cutaneous symptoms. It's crucial to understand that while antihistamines are beneficial for symptom management, they do not replace the need for epinephrine in treating anaphylaxis. The study 1 highlights the importance of not delaying epinephrine administration for antihistamines, emphasizing the role of antihistamines as adjunctive therapy.

From the FDA Drug Label

INDICATIONS AND USAGE: Diphenhydramine hydrochloride in the injectable form is effective in adults and pediatric patients, other than premature infants and neonates, for the following conditions when diphenhydramine hydrochloride in the oral form is impractical Antihistaminic 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, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.

The antihistamine given in anaphylaxis shock is diphenhydramine (IV), as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled 2. Key points:

  • Diphenhydramine is used for amelioration of allergic reactions in anaphylaxis.
  • It is administered intravenously (IV).
  • It is used as an adjunct to epinephrine and other standard measures.

From the Research

Antihistamine Treatment in Anaphylaxis

  • The primary treatment for anaphylaxis is epinephrine, as it is the most effective medication for relieving symptoms and preventing fatalities 3, 4, 5.
  • Antihistamines, such as diphenhydramine, are sometimes used as adjunctive therapy in anaphylaxis, but they are not a replacement for epinephrine 6, 7, 5.
  • H1-antihistamines, such as diphenhydramine, can help relieve symptoms of anaphylaxis, but they have a slower onset of action compared to epinephrine and cannot block all the effects of histamine release 6.
  • Some studies suggest that antihistamines may be beneficial in preventing anaphylaxis in patients at risk, and they may be used in combination with epinephrine for treatment 6, 7.

Specific Antihistamines Used in Anaphylaxis

  • Diphenhydramine is a commonly used antihistamine in anaphylaxis treatment, but it is not a substitute for epinephrine 4, 7.
  • Newer antihistamines with fewer side effects may be more effective in treating anaphylaxis, but more research is needed to determine their role in treatment 6.

Importance of Epinephrine in Anaphylaxis Treatment

  • Epinephrine is the first-line treatment for anaphylaxis and should be administered promptly to prevent fatalities 3, 4, 5.
  • Delayed epinephrine administration can increase the risk of fatal anaphylaxis, and antihistamines should not be used as a replacement for epinephrine 7, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Epinephrine (adrenaline) in anaphylaxis.

Chemical immunology and allergy, 2010

Research

Histamine and antihistamines in anaphylaxis.

Clinical allergy and immunology, 2002

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

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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