What is the best second-generation antihistamine (antihistamine of choice)?

Best Second-Generation Antihistamine for Allergic Rhinitis

Among second-generation antihistamines, fexofenadine is the preferred choice due to its non-sedating properties at all doses and favorable safety profile. 1, 2

Comparison of Second-Generation Antihistamines

Sedation Properties

• Fexofenadine, loratadine, and desloratadine do not cause sedation at recommended doses 3
• Loratadine and desloratadine may cause sedation at doses exceeding the recommended dose 3
• Cetirizine and intranasal azelastine may cause sedation at recommended doses 3
• Fexofenadine maintains its non-sedating properties even at higher than FDA-approved doses, making it truly non-sedating 3, 2

Blood-Brain Barrier Penetration

• Fexofenadine has decreased blood-brain barrier permeability, which explains its non-sedating properties 4
• PET studies confirm zero H1-receptor occupancy in the brain with fexofenadine, confirming its inability to cross the blood-brain barrier 2

Efficacy

• Among the newer, non-sedating antihistamines, no single agent has been conclusively found to achieve superior overall response rates 3, 5
• All second-generation antihistamines effectively alleviate symptoms of allergic rhinitis 6
• Fexofenadine effectively relieves both nasal and ocular symptoms of allergic rhinitis 4

Special Populations

Children

• Fexofenadine displays a favorable safety profile in children compared with other second-generation antihistamines 4
• Second-generation antihistamines are generally preferred over first-generation antihistamines for children due to reduced sedation and cognitive impairment 6

Elderly

• Older adults are more sensitive to psychomotor impairment from antihistamines 3
• Non-sedating antihistamines like fexofenadine are particularly preferred in elderly patients to avoid falls, fractures, and cognitive impairment 6

Clinical Decision Algorithm

1. First choice: Fexofenadine

   • Truly non-sedating at all doses 1, 2
   • No impairment of cognitive/psychomotor function 7, 2
   • Effective for both nasal and ocular symptoms 4

2. Second choice: Loratadine or desloratadine

   • Non-sedating at recommended doses 3
   • May cause sedation at higher doses 3

3. Third choice: Cetirizine or levocetirizine

   • May cause mild sedation at recommended doses 3, 5
   • Potentially more effective than loratadine for symptom reduction 5

Common Pitfalls to Avoid

• Avoid first-generation antihistamines (diphenhydramine, chlorpheniramine) due to significant sedation, performance impairment, and anticholinergic effects 3, 7
• Remember that second-generation antihistamines have limited effect on nasal congestion; consider intranasal corticosteroids for better control of this symptom 1, 6
• Be cautious with standard doses of loratadine or desloratadine in patients with low body mass, as they may experience sedation due to higher relative dosing 3
• Don't assume all second-generation antihistamines have the same sedation profile; there are important differences 3

Important Considerations

• Intranasal corticosteroids are more effective than oral antihistamines for overall control of allergic rhinitis symptoms, particularly nasal congestion 6, 5
• Continuous treatment with antihistamines is more effective than intermittent use for seasonal or perennial allergic rhinitis 6
• For patients with both allergic rhinitis and asthma, consider leukotriene receptor antagonists (e.g., montelukast) in addition to antihistamines 5

In conclusion, while all second-generation antihistamines are effective for allergic rhinitis symptoms, fexofenadine offers the advantage of being truly non-sedating at all doses, making it the preferred choice for most patients, particularly those who need to remain alert and those at higher risk for sedation-related complications.