What are the recommended 2nd generation antihistamines (second-generation antihistamines) for treating allergic reactions?

Recommended Second-Generation Antihistamines for Allergic Reactions

For treating allergic reactions, second-generation antihistamines such as fexofenadine, loratadine, and desloratadine are preferred due to their minimal sedative effects at recommended doses, while cetirizine and intranasal azelastine should be used with caution due to their potential sedative properties. 1

First-Line Second-Generation Antihistamines

The following second-generation antihistamines are recommended based on their sedation profile:

Non-sedating at recommended doses:

• Fexofenadine: Remains non-sedating even at higher than FDA-approved doses 1
• Loratadine: Non-sedating at standard 10mg dose 1
• Desloratadine: Non-sedating at recommended doses 1

May cause sedation:

• Cetirizine: Associated with mild drowsiness in about 13.7% of patients (compared to 6.3% with placebo) 1
• Intranasal azelastine: May cause somnolence in approximately 11.5% of patients 1

Clinical Decision Algorithm

1. For most patients with allergic reactions:

   • Start with fexofenadine (most consistently non-sedating)
   • Alternatives: loratadine or desloratadine

2. For patients with severe rhinorrhea despite antihistamine use:

   • Consider adding intranasal anticholinergic (ipratropium bromide) rather than switching to a first-generation antihistamine 1

3. For patients needing nighttime symptom control:

   • Consider cetirizine (mild sedation may be beneficial at night)
   • Avoid first-generation antihistamines even at bedtime, as they can cause next-day impairment 1

4. For patients with allergic reactions during medical procedures (e.g., IV iron infusions):

   • Loratadine 10mg PO or cetirizine 10mg IV/PO are recommended for managing urticaria 1

Important Clinical Considerations

Efficacy

• No single second-generation antihistamine has been conclusively found to achieve superior overall response rates 1
• All are effective for allergic rhinitis and urticaria at recommended doses

Safety Concerns

• Avoid first-generation antihistamines (diphenhydramine, chlorpheniramine, etc.) due to:
  • Significant sedation and performance impairment
  • Anticholinergic effects (dry mouth, constipation, urinary retention)
  • Increased risk of falls and cognitive impairment, especially in older adults 1
  • Potential for impaired learning and school performance in children 2

Special Populations

• Older adults: Use fexofenadine, loratadine, or desloratadine to minimize sedation and anticholinergic effects 1
• Drivers/workers: Avoid cetirizine and first-generation antihistamines due to performance impairment risks 1, 2
• Patients with asthma: Second-generation antihistamines are safe and do not alter pulmonary function 3

Common Pitfalls to Avoid

1. AM/PM dosing regimen: Combining a second-generation antihistamine in the morning with a first-generation at night is NOT recommended, as first-generation agents have prolonged half-lives causing next-day impairment 1

2. Dose-related sedation: Loratadine and desloratadine can cause sedation at higher than recommended doses, particularly in patients with low body mass 1

3. Underestimating impairment: Patients may deny sedation with antihistamines while still experiencing performance impairment 2

4. Drug interactions: Be aware of potential interactions, particularly with medications that affect QTc interval 3

Second-generation antihistamines represent a significant advancement over first-generation agents due to their improved safety profile while maintaining efficacy for allergic conditions.