What second-generation antihistamines (SGAs) have sedating effects?

Sedating Second-Generation Antihistamines

Cetirizine and intranasal azelastine are the second-generation antihistamines that have sedating effects at recommended doses, while loratadine and desloratadine may cause sedation at doses exceeding the recommended dose. 1

Sedation Potential of Second-Generation Antihistamines

Second-generation antihistamines have varying degrees of sedation potential:

• Non-sedating at recommended doses:

  • Fexofenadine (1.3% sedation potential)
  • Desloratadine (2.1% sedation potential at recommended doses)
  • Loratadine (8% sedation potential at recommended doses)

• Potentially sedating:

  • Cetirizine (mildly sedative at recommended doses)
  • Intranasal azelastine (can cause sedation at recommended doses)
  • Loratadine and desloratadine (may cause sedation at doses exceeding recommendations) 1, 2

Clinical Implications of Sedation

The sedative effects of second-generation antihistamines are significantly less pronounced than first-generation antihistamines like diphenhydramine (50% sedation potential) or hydroxyzine (80% sedation potential) 2. However, clinicians should be aware that:

• Even mild sedation can impact driving performance and occupational safety
• Concomitant use of other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) may enhance performance impairment 1
• Elderly patients are more sensitive to psychomotor impairment and at increased risk for complications like falls 1, 2

Patient Selection Considerations

When prescribing second-generation antihistamines, consider:

1. Patient age: Elderly patients are more vulnerable to sedative effects 1, 2

2. Comorbidities: Use caution in patients with:

   • Prostatic hyperplasia (risk of urinary retention)
   • Glaucoma
   • Cognitive impairment
   • Cardiovascular disease 2

3. Occupation: Patients who operate machinery or drive professionally should preferentially receive non-sedating options 1

4. Renal function: For severe renal impairment, loratadine or desloratadine should be used with caution 2

Evidence Quality and Limitations

The evidence regarding sedation with second-generation antihistamines shows some variability. A meta-analysis found that while second-generation antihistamines caused less sedation than diphenhydramine, they still showed a mild but statistically significant sedating effect compared to placebo 3. This suggests that the distinction between "sedating" and "non-sedating" antihistamines is not absolute.

Some studies indicate that individual sensitivity to the sedative effects varies considerably, and laboratory studies may not always predict real-world performance impairment 4. Additionally, disease-induced sedation or reduced drug clearance may enhance sedative effects in clinical practice 4.

Clinical Recommendations

1. For patients where sedation must be avoided:

   • Fexofenadine is the preferred option with the lowest sedation potential (1.3%) 2, 5
   • Loratadine at recommended doses is also appropriate (8% sedation potential) 2

2. For patients where mild sedation is acceptable or beneficial:

   • Cetirizine may be appropriate, though it has been shown to impair performance to a lesser degree than first-generation antihistamines 5

3. For elderly patients:

   • Avoid first-generation antihistamines entirely
   • Prefer fexofenadine or loratadine at recommended doses
   • Use cetirizine with caution 2

4. For patients with renal impairment:

   • Loratadine or desloratadine with appropriate dose adjustments 2

By understanding the varying sedation profiles of second-generation antihistamines, clinicians can select the most appropriate agent based on patient characteristics and clinical needs.