Does azelastine (nasal spray) cross the blood-brain barrier?

Azelastine Nasal Spray and Blood-Brain Barrier Penetration

Yes, azelastine nasal spray does cross the blood-brain barrier, which explains why somnolence is reported in approximately 11.5% of patients using the standard dose. 1

Mechanism and CNS Effects

Azelastine is a second-generation antihistamine available as a nasal spray for treating allergic and non-allergic rhinitis. Despite being administered topically, it has systemic absorption with a bioavailability of about 40% 2. This systemic absorption allows azelastine to cross the blood-brain barrier, though to a lesser extent than first-generation antihistamines.

Evidence of CNS Penetration:

• Clinical trials of nasal azelastine report somnolence in 11.5% of patients at the standard dose (2 sprays per nostril twice daily) 1
• The 2008 rhinitis practice parameter specifically notes that azelastine has sedative properties compared to placebo 1
• When used at a lower dose of 1 spray per nostril twice daily, somnolence rates decrease significantly to 0.4% 3

Comparison with Other Antihistamines

Azelastine's CNS effects are positioned between non-sedating second-generation oral antihistamines and highly sedating first-generation antihistamines:

• First-generation antihistamines (e.g., diphenhydramine): High blood-brain barrier penetration with significant sedation
• Azelastine nasal spray: Moderate blood-brain barrier penetration with mild-to-moderate sedation (11.5% at standard dose)
• Non-sedating oral antihistamines (e.g., fexofenadine, loratadine, desloratadine): Minimal blood-brain barrier penetration with little to no sedation at recommended doses

Clinical Implications

The blood-brain barrier penetration of azelastine has important clinical implications:

• Patient counseling: Patients should be warned about the potential for drowsiness when starting azelastine nasal spray 1
• Dose considerations: Using the lower dose of 1 spray per nostril twice daily significantly reduces somnolence (0.4% vs 11.5%) while maintaining efficacy 3
• Monitoring: Follow-up is advised to assess response and side effects, particularly signs of somnolence 1
• Comparison with other intranasal antihistamines: Olopatadine nasal spray has a lower reported somnolence rate (0.9%) compared to azelastine (11.5%) 1

Practical Recommendations

For patients requiring intranasal antihistamine therapy:

• Start with the lower effective dose (1 spray per nostril twice daily) to minimize CNS effects
• Advise patients about the potential for drowsiness, especially when first starting treatment
• Consider olopatadine as an alternative if sedation with azelastine is problematic
• Avoid combining with other medications that cause CNS depression
• Exercise caution when prescribing to patients who operate machinery or vehicles

Common Pitfalls to Avoid

• Underestimating sedation potential: Despite being a second-generation antihistamine, azelastine's CNS effects are more pronounced than many oral second-generation options
• Incorrect dosing technique: Proper administration technique can reduce bitter taste, which is the most common side effect (19.7%) 1
• Overlooking drug interactions: Be cautious about combining with other CNS depressants

In summary, azelastine nasal spray does cross the blood-brain barrier, resulting in potential sedation, though to a lesser extent than first-generation antihistamines. Using the lowest effective dose can minimize these CNS effects while maintaining therapeutic benefit.