Systemic Absorption of Azelastine Nasal Spray
Yes, azelastine nasal spray is absorbed systemically with approximately 40% bioavailability after intranasal administration. 1
Pharmacokinetic Profile
Azelastine nasal spray demonstrates significant systemic absorption with the following characteristics:
- Bioavailability: Approximately 40% of the administered dose enters systemic circulation 1
- Time to maximum concentration (Cmax): Achieved in 2-3 hours after intranasal administration 1
- Elimination half-life: 22 hours 1
- Plasma protein binding: Approximately 88% for azelastine and 97% for its active metabolite desmethylazelastine 1
- Metabolism: Oxidatively metabolized to desmethylazelastine by the cytochrome P450 enzyme system 1
Clinical Implications of Systemic Absorption
The systemic absorption of azelastine has several important clinical implications:
Side Effects Related to Systemic Absorption
- Somnolence: Reported in 11.5% of patients using the standard dose of 2 sprays per nostril twice daily 2, but significantly lower (0.4%) with reduced dosing of 1 spray per nostril twice daily 3
- Bitter taste: Occurs in 19.7% of patients at standard dosing 3, but reduced to 8.3% with lower dosing regimens
- Skin test inhibition: Can inhibit skin test reactions due to systemic antihistamine effects 2
Drug Interactions
- CYP450 interactions: Although specific P450 isoforms responsible for azelastine biotransformation haven't been identified, studies with CYP3A4 inhibitor erythromycin showed no significant pharmacokinetic interaction 1
- Non-specific P450 inhibitors: Cimetidine (400 mg twice daily) increased oral azelastine concentrations by approximately 65% 1
Dosing Considerations
The systemic absorption profile supports the following dosing approaches:
- Standard dosing: 2 sprays per nostril twice daily for patients ≥12 years; 1 spray per nostril twice daily for children 6-11 years 2
- Reduced dosing option: 1 spray per nostril twice daily may be considered for adults to minimize systemic side effects while maintaining efficacy 3
Special Populations
- Renal insufficiency: Oral studies show 70-75% higher Cmax and AUC in patients with creatinine clearance <50 mL/min 1
- Hepatic impairment: Pharmacokinetics not significantly influenced based on oral administration studies 1
- Age and gender: Do not significantly influence pharmacokinetics 1
Clinical Advantages Despite Systemic Absorption
Despite systemic absorption, intranasal azelastine offers several advantages:
- Rapid onset of action: Clinical effects begin within 15 minutes 2
- Duration of action: 12-24 hours, allowing for twice-daily dosing 4
- Efficacy for nasal congestion: Unlike many oral antihistamines, intranasal azelastine can reduce nasal congestion 4
Conclusion
Azelastine nasal spray undergoes significant systemic absorption, which explains both its therapeutic effects and potential side effects like somnolence. Clinicians should be aware of this systemic absorption when prescribing azelastine, particularly in patients with renal impairment or those taking medications that might interact with the cytochrome P450 system.