What are the first-line antihistamines for treating allergic reactions?

First-Line Antihistamines for Allergic Reactions

Second-generation antihistamines are generally preferred over first-generation antihistamines as first-line treatment for allergic reactions due to their improved safety profile and reduced sedative effects. 1

Classification of Antihistamines

First-Generation Antihistamines

• Diphenhydramine (Benadryl): 25-50 mg oral or IV
  • Effective but causes significant sedation and cognitive impairment
  • Used in acute allergic reactions and anaphylaxis as adjunctive therapy
  • Should not be substituted for epinephrine in anaphylaxis 1

Second-Generation Antihistamines

• Cetirizine (Zyrtec): 10 mg daily 2

  • Relatively rapid onset of action compared to other second-generation options
  • May cause mild sedation at recommended doses
  • Approved for ages 6 years and older 2

• Levocetirizine (Xyzal): 5 mg daily 3

  • Provides 24-hour relief of allergic symptoms
  • Effective for sneezing, runny nose, itchy nose/throat, and itchy watery eyes

• Fexofenadine (Allegra): 120-180 mg daily

  • Non-sedating even at higher than recommended doses
  • Slightly slower onset of action than cetirizine 4

• Loratadine (Claritin): 10 mg daily

  • Non-sedating at recommended doses
  • May cause sedation at doses exceeding recommendations 1

• Desloratadine (Clarinex): 5 mg daily

  • Non-sedating at recommended doses
  • May cause sedation at doses exceeding recommendations 1

Treatment Algorithm for Allergic Reactions

Mild to Moderate Allergic Reactions (Allergic Rhinitis, Urticaria)

1. First-line: Second-generation antihistamines

   • Fexofenadine, loratadine, or desloratadine for patients where sedation is a concern
   • Cetirizine when faster onset of action is needed (though may cause mild sedation)

2. Alternative options:

   • Intranasal antihistamines (e.g., azelastine) for predominant nasal symptoms
   • May be used as first-line treatment for allergic and nonallergic rhinitis 1
   • Note: Intranasal antihistamines may cause sedation and can inhibit skin test reactions 1

Severe Allergic Reactions (Anaphylaxis)

1. First-line: Epinephrine IM (not antihistamines)

2. Adjunctive therapy:

   • H1 antihistamine: Diphenhydramine 1-2 mg/kg (max 50 mg) IV or oral
   • Alternative: Less-sedating second-generation antihistamine such as cetirizine 10 mg 1
   • H2 antihistamine: Ranitidine 1-2 mg/kg (max 75-150 mg) oral or IV 1

Important Clinical Considerations

1. Efficacy vs. Sedation Trade-off:

   • Second-generation antihistamines are less sedating but may have slightly delayed onset compared to first-generation options 4, 5
   • The small difference in onset time is outweighed by the significant reduction in sedation and impairment 5

2. Special Populations:

   • Avoid first-generation antihistamines in elderly patients due to anticholinergic effects
   • Use caution with sedating antihistamines in patients who need to drive or operate machinery
   • For children, second-generation options are preferred to avoid sedation and cognitive impairment

3. Common Pitfalls:

   • Using antihistamines alone for anaphylaxis (epinephrine is first-line)
   • Overlooking that antihistamines only relieve itching and urticaria but do not treat stridor, shortness of breath, wheezing, GI symptoms, or shock 1
   • Failing to recognize that first-generation antihistamines can worsen cognitive function and mask symptoms of anaphylaxis progression 6

4. Dosing Considerations:

   • Higher doses of second-generation antihistamines may be needed to achieve equivalent antihistaminic effects to first-generation options 7
   • First-generation antihistamines should be used with caution due to their significant side effect profile 6

By following this evidence-based approach to antihistamine selection, clinicians can effectively manage allergic reactions while minimizing adverse effects and optimizing patient outcomes.