Second-Line Treatment for Allergic Reactions

Introduction to Second-Line Treatments

• The American Academy of Allergy, Asthma, and Immunology recommends second-line treatment for allergic reactions, including H1 antihistamines, H2 antihistamines, and corticosteroids, which should be administered after epinephrine in cases of anaphylaxis 1, 2

H1 Antihistamines

• Diphenhydramine is the most commonly used H1 antihistamine for allergic reactions, administered at 1-2 mg/kg per dose with a maximum dose of 50 mg IV or oral, as recommended by the American Academy of Allergy, Asthma, and Immunology 1
• For ongoing management after discharge, diphenhydramine should be continued every 6 hours for 2-3 days, according to the American Academy of Allergy, Asthma, and Immunology 2
• H1 antihistamines should never be used alone in the treatment of anaphylaxis, as they have a much slower onset of action than epinephrine, as stated by the American Academy of Allergy, Asthma, and Immunology 3

H2 Antihistamines

• Ranitidine is the preferred H2 antihistamine, administered at 1-2 mg/kg per dose with a maximum dose of 75-150 mg oral or IV, as recommended by the American Academy of Allergy, Asthma, and Immunology 2
• The combination of H1 and H2 antihistamines works better than either one alone, according to the American Academy of Allergy, Asthma, and Immunology 4

Corticosteroids

• Prednisone is recommended at 1 mg/kg with a maximum dose of 60-80 mg orally, as stated by the American Academy of Allergy, Asthma, and Immunology 2
• Corticosteroids are primarily used to prevent recurrent or protracted anaphylaxis, although there is no clear evidence to support such therapy, according to the American Academy of Allergy, Asthma, and Immunology 5

Important Considerations

• These second-line treatments should only be administered after epinephrine in cases of anaphylaxis, as recommended by the American Academy of Allergy, Asthma, and Immunology 1, 2

Special Situations

• For patients on beta-blockers who may have reduced response to epinephrine, glucagon should be available as an additional treatment option, according to the American Academy of Allergy, Asthma, and Immunology 4
• In patients with refractory hypotension, glucagon can be administered at 20-30 μg/kg for children or 1-5 mg for adults, as stated by the American Academy of Allergy, Asthma, and Immunology 2

Follow-up Care

• After an allergic reaction, especially anaphylaxis, patients should have a follow-up appointment with their primary care physician, as recommended by the American Academy of Allergy, Asthma, and Immunology 1
• Patients should receive education on allergen avoidance and an anaphylaxis emergency action plan, according to the American Academy of Allergy, Asthma, and Immunology 6
• For patients at risk of recurrent anaphylaxis, prescribe an epinephrine auto-injector (2 doses) with proper training on its use, as stated by the American Academy of Allergy, Asthma, and Immunology 2

Management of Allergic Reactions with Famotidine

Role of H2 Antihistamines in Allergic Reactions

• The American Academy of Allergy, Asthma, and Immunology recommends H2 antihistamines like famotidine as adjunctive therapy for allergic reactions, and should not be substituted for first-line treatments 7, 8
• Minimal evidence supports the use of H2 antihistamines alone in the emergency treatment of anaphylaxis, according to the American Academy of Allergy, Asthma, and Immunology 7, 8

Proper Treatment Algorithm for Allergic Reactions

First-line Treatment

• The American College of Allergy, Asthma, and Immunology states that epinephrine is the only first-line treatment for anaphylaxis with no substitute 9
• The American Heart Association recommends epinephrine administration immediately for severe allergic reactions (diffuse hives, shortness of breath, respiratory symptoms, obstructive swelling, or circulatory symptoms) 10

Second-line/Adjunctive Treatments

• The American Academy of Allergy, Asthma, and Immunology suggests H1 antihistamines (e.g., diphenhydramine) for relieving itching and urticaria 7, 10
• The American College of Allergy, Asthma, and Immunology recommends H2 antihistamines (e.g., famotidine, ranitidine) may be used concurrently with H1 antihistamines 7

Important Cautions

• The American Academy of Allergy, Asthma, and Immunology warns that using antihistamines (including H2 blockers) as the primary treatment is the most common reason reported for not using epinephrine and may place patients at significantly increased risk for progression toward life-threatening reactions 9

Best Practice Recommendations

• The American College of Allergy, Asthma, and Immunology recommends that for severe allergic reactions/anaphylaxis: Epinephrine first, followed by H1 antihistamines, H2 antihistamines, and corticosteroids as adjunctive therapy 7, 11
• The American Heart Association advises to never delay epinephrine administration to give antihistamines in cases of anaphylaxis 9

Anaphylaxis Treatment Guidelines

Diagnosis and Initial Treatment

• The American Academy of Allergy, Asthma, and Immunology states that anaphylaxis involves 2 or more body systems and can be life-threatening, with symptoms including respiratory difficulty, cutaneous manifestations, and gastrointestinal symptoms 12
• Patients with asthma are at particularly high risk for fatal anaphylaxis, and the presence of wheezing in an asthmatic patient having an allergic reaction is especially concerning and mandates immediate epinephrine 13
• The American Academy of Allergy, Asthma, and Immunology recommends that patients with severe uncontrolled asthma be considered high-risk patients requiring heightened vigilance, although specific guidance is not provided in this context 12

Epinephrine Administration

• If patient weighs >25 kg: 0.3 mg epinephrine autoinjector IM (anterior-lateral thigh) 13
• If patient weighs 10-25 kg: 0.15 mg epinephrine autoinjector IM (anterior-lateral thigh) 13
• Alternative: Epinephrine 1:1,000 solution at 0.01 mg/kg IM, maximum 0.5 mg per dose 13
• May repeat every 5-15 minutes if symptoms persist 13

Adjunctive Therapy

• Albuterol nebulizer: 1.5 mL (child) or 3 mL (adult) every 20 minutes or continuously as needed for persistent wheezing 13
• Diphenhydramine: 1-2 mg/kg IV or oral, maximum 50 mg (oral liquid absorbs faster than tablets) 13, 14
• H2 antihistamine (ranitidine): 1-2 mg/kg, maximum 75-150 mg IV or oral 14
• Supplemental oxygen 13
• Place patient recumbent with lower extremities elevated if tolerated 13

Corticosteroids

• Methylprednisolone 1 mg/kg IV, maximum 60-80 mg OR 14
• Prednisone 1 mg/kg oral, maximum 60-80 mg 13

Discharge Planning

• Prescribe two epinephrine autoinjectors at discharge 13, 14
• Continue diphenhydramine every 6 hours for 2-3 days 13
• Continue H2 antihistamine twice daily for 2-3 days 13
• Continue prednisone daily for 2-3 days 13
• Refer to allergist for identification of trigger and consideration of immunotherapy if indicated 13

Anaphylaxis and Allergic Reaction Management

Introduction to Treatment Options

• The American Academy of Allergy, Asthma, and Immunology recommends choosing IM diphenhydramine when oral therapy is impractical or impossible, such as in patients with severe vomiting, altered mental status, or inability to swallow; otherwise, oral cetirizine is preferred for mild-to-moderate allergic reactions due to comparable efficacy with fewer sedative effects 15

First-Line Treatment for Anaphylaxis

• The American Academy of Allergy, Asthma, and Immunology states that first-line treatment is always IM epinephrine (0.01 mg/kg, max 0.3-0.5 mg in anterolateral thigh) - diphenhydramine and cetirizine are both adjunctive therapies only and should never replace epinephrine 16, 17

Adjunctive Therapy for Anaphylaxis

• The American Academy of Allergy, Asthma, and Immunology recommends that after epinephrine administration, diphenhydramine can be given IV or IM (1-2 mg/kg, max 50 mg) for more rapid effect in the acute setting 16

Post-Treatment Considerations

• The American Academy of Allergy, Asthma, and Immunology suggests that after treating severe reactions with parenteral diphenhydramine, continue oral diphenhydramine every 6 hours for 2-3 days to prevent biphasic reactions, or use non-sedating second-generation antihistamines instead of continued diphenhydramine 16
• The American Academy of Allergy, Asthma, and Immunology recommends an observation period of 4-6 hours minimum after anaphylaxis treatment regardless of which antihistamine is used 16

Choice of Antihistamine

• The American Academy of Allergy, Asthma, and Immunology states that second-generation antihistamines like cetirizine are generally preferred over first-generation antihistamines because they cause less sedation, performance impairment, and anticholinergic effects 15
• The American Academy of Allergy, Asthma, and Immunology notes that IM diphenhydramine carries risks of rapid IV administration including potential cardiovascular effects when given too quickly (should not exceed 25 mg/min) 16