What is the recommended dosage and treatment plan for antihistamines (anti-histamine medications) in patients with allergic reactions?

Antihistamine Dosing and Treatment for Allergic Reactions

Antihistamines are strictly adjunctive therapy and must never be used as first-line treatment or substituted for epinephrine in anaphylaxis—they only relieve itching and urticaria, not life-threatening symptoms like stridor, bronchospasm, hypotension, or shock. 1

Critical First Principle: Epinephrine First in Anaphylaxis

Epinephrine is the only first-line treatment for anaphylaxis and must be administered immediately via intramuscular injection (0.01 mg/kg, maximum 0.5 mg) before any antihistamine is given. 1, 2 Antihistamines have no effect on airway edema, respiratory distress, gastrointestinal symptoms, or cardiovascular collapse. 1

H1 Antihistamine Dosing for Acute Allergic Reactions

First-Generation H1 Antihistamines (Diphenhydramine)

For acute treatment:

• Adults: 25-50 mg IV or IM 1, 2
• Pediatrics: 1-2 mg/kg per dose (maximum 50 mg) IV, IM, or oral 1, 2, 3
• Oral liquid formulation is preferred over tablets for faster absorption 1, 3

For post-discharge continuation:

• Diphenhydramine every 6 hours for 2-3 days 1, 3

Second-Generation H1 Antihistamines (Less Sedating Alternatives)

Cetirizine 10 mg orally is the preferred second-generation option due to relatively rapid onset compared to other non-sedating agents. 1 This avoids the sedation, cognitive impairment, and decreased awareness of worsening symptoms associated with first-generation agents. 1

• Adults: Cetirizine 10 mg once daily 4
• Alternative: Fexofenadine 180 mg orally (though onset may be marginally slower than diphenhydramine) 5

H2 Antihistamine Combination Therapy

Adding an H2 antihistamine (ranitidine or famotidine) to H1 therapy is superior to H1 monotherapy for managing anaphylaxis, though evidence is limited. 2

Dosing:

• Adults: Ranitidine 50 mg IV or 75-150 mg oral 1, 2
• Pediatrics: Ranitidine 1-2 mg/kg per dose (maximum 75-150 mg) 1, 2, 3
• Post-discharge: H2 antihistamine twice daily for 2-3 days 1, 3

Treatment Algorithm by Severity

Mild Allergic Reactions (Urticaria, Flushing, Isolated Mild Angioedema)

Start with H1 antihistamine alone, but maintain close observation for progression to anaphylaxis. 1

• Diphenhydramine 25-50 mg (adults) or 1-2 mg/kg (pediatrics) 1
• If any progression occurs or patient has history of prior severe reactions, administer epinephrine immediately 1, 3

Anaphylaxis (Any Respiratory, Cardiovascular, or Multi-System Involvement)

Immediate IM epinephrine is mandatory—antihistamines are only adjunctive. 1, 2

Treatment sequence:

1. Epinephrine IM (anterior-lateral thigh): 0.01 mg/kg, maximum 0.5 mg; may repeat every 5-15 minutes 1, 2
2. Place patient recumbent with legs elevated 1
3. Adjunctive H1 antihistamine: Diphenhydramine 1-2 mg/kg (maximum 50 mg) IV or oral 1, 2
4. Adjunctive H2 antihistamine: Ranitidine 1-2 mg/kg (maximum 75-150 mg) 1, 2
5. Bronchodilator if needed: Albuterol nebulized (child 1.5 mL, adult 3 mL) or MDI (child 4-8 puffs, adult 8 puffs) 1
6. Corticosteroid: Prednisone 1 mg/kg (maximum 60-80 mg) or methylprednisolone 1 mg/kg IV 1
7. IV fluids in large volumes for hypotension or incomplete response to epinephrine 1

Observation and Discharge Planning

All patients receiving epinephrine must be observed for 4-6 hours minimum, with prolonged observation for severe or refractory symptoms. 1

Discharge regimen includes:

• Two epinephrine auto-injectors with training 1
• H1 antihistamine (diphenhydramine every 6 hours or non-sedating alternative) for 2-3 days 1, 3
• H2 antihistamine (ranitidine twice daily) for 2-3 days 1, 3
• Corticosteroid (prednisone daily) for 2-3 days 1
• Written anaphylaxis emergency action plan 1
• Follow-up with allergist/immunologist 1

Chronic Urticaria Management

For chronic spontaneous urticaria, start with standard-dose second-generation H1 antihistamine, then uptitrate up to 4-fold if inadequate control after 2-4 weeks. 1

• Initial: Standard dose second-generation antihistamine (e.g., cetirizine 10 mg daily) 1
• If inadequate control: Increase up to 4-fold (e.g., cetirizine 40 mg daily) 1
• If still inadequate: Add omalizumab 300 mg every 4 weeks 1
• Step-down only after 3 consecutive months of complete control, reducing by no more than 1 tablet per month 1

Critical Pitfalls to Avoid

• Never delay epinephrine administration to "try antihistamines first" in suspected anaphylaxis—this increases mortality risk 2, 3
• Never use antihistamines as monotherapy for any reaction involving respiratory or cardiovascular symptoms 1, 2
• First-generation antihistamines cause sedation that may mask worsening symptoms and impair recognition of progression 1, 6
• Oral tablets absorb more slowly than liquid formulations—use liquid in children for accurate weight-based dosing 1, 3
• Antihistamines do not relieve laryngeal edema or bronchospasm—albuterol and epinephrine are required 1