Management of Diphenhydramine Allergy

Acute Management

The American College of Allergy, Asthma, and Immunology recommends stopping diphenhydramine administration immediately and maintaining intravenous access if the drug was given parenterally, as well as assessing airway, breathing, circulation (ABCs) and level of consciousness in patients with a documented allergy to diphenhydramine 1
For anaphylaxis to diphenhydramine, the American Heart Association recommends administering epinephrine 0.01 mg/kg intramuscularly (1:1000 dilution, maximum 0.5 mg) into the lateral thigh immediately, with repeat doses every 5-15 minutes as needed 1, 2
The American College of Emergency Physicians suggests providing rapid fluid resuscitation with 1-2 liters normal saline at 5-10 mL/kg in the first 5 minutes for patients with anaphylaxis to diphenhydramine 1
The American Academy of Allergy, Asthma, and Immunology advises against using diphenhydramine or any other H1-antihistamine that cross-reacts in patients with a documented allergy to diphenhydramine, and recommends considering H2-antihistamine (ranitidine 50 mg IV or famotidine) instead 1, 2
The National Institute of Allergy and Infectious Diseases recommends administering corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours) to prevent biphasic reactions in patients with anaphylaxis to diphenhydramine 1, 2

The Joint Commission recommends documenting the specific reaction type (urticaria, anaphylaxis, other), severity grade, timing, and management provided in patients with a documented allergy to diphenhydramine 1