AZELASTINE HYDROCHLORIDE CHILDREN'S ALLERGY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZELASTINE HYDROCHLORIDE CHILDREN'S ALLERGY (AZELASTINE HYDROCHLORIDE CHILDREN'S ALLERGY).
Azelastine hydrochloride is a phthalazinone derivative that acts as a selective histamine H1-receptor antagonist. It inhibits the release of histamine and other mediators from mast cells, reduces chemotaxis, and decreases eosinophil activation. It also suppresses leukotriene and cytokine production.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) enzymes, mainly CYP3A4 and CYP2D6, to its major metabolite N-desmethylazelastine. Also undergoes oxidative metabolism. Oral bioavailability is low due to extensive first-pass metabolism. |
| Excretion | Primarily renal (approximately 75%), with about 50% as unchanged drug and 25% as metabolites via CYP3A4 and CYP2D6. Fecal excretion accounts for ~20%. |
| Half-life | Terminal elimination half-life is 22–25 hours in adults; steady state achieved in 3–5 days. In children (6–11 years), half-life is similar (mean 22 hours). |
| Protein binding | Approximately 88–92%, primarily to albumin. |
| Volume of Distribution | Approximately 14.5 L/kg (14.5 ± 5.4 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Intranasal: absolute bioavailability ~40% due to first-pass metabolism; oral bioavailability is ~6% due to extensive presystemic clearance. |
| Onset of Action | Intranasal: symptom relief within 30 minutes to 1 hour; ophthalmic: within 3 minutes. |
| Duration of Action | Intranasal: 12 hours (twice daily dosing recommended); ophthalmic: 8–12 hours (up to 4 times daily). Clinical effect may persist for several hours after the last dose. |
Azelastine hydrochloride nasal spray: 1 spray (137 mcg) per nostril twice daily; maximum 2 sprays per nostril twice daily.
| Dosage form | SPRAY, METERED |
| Renal impairment | No specific GFR-based dose adjustments recommended; use with caution in severe renal impairment. |
| Liver impairment | No specific Child-Pugh based dose adjustments recommended. |
| Pediatric use | Children 6–11 years: 1 spray (137 mcg) per nostril twice daily. Children 12 years and older: same as adult dosing. |
| Geriatric use | No specific dose adjustment; elderly patients may be more sensitive to adverse effects; use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZELASTINE HYDROCHLORIDE CHILDREN'S ALLERGY (AZELASTINE HYDROCHLORIDE CHILDREN'S ALLERGY).
| Breastfeeding | Not known if azelastine is excreted in human breast milk. In animal studies, azelastine and its metabolites appeared in rat milk at levels similar to maternal plasma. M/P ratio: not determined. Due to potential for serious adverse reactions in nursing infants, consider importance of drug to mother and discontinue nursing or discontinue drug. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate well-controlled studies in pregnant women. In animal studies, azelastine hydrochloride was not teratogenic in rats or rabbits at oral doses up to 30 mg/kg/day (approximately 250 times the maximum recommended human daily intranasal dose on a mg/m² basis). However, embryocidal effects and delayed ossification were observed at doses ≥ 2.5 mg/kg/day in rats. Use during pregnancy only if potential benefit justifies potential risk to the fetus. First trimester: risk cannot be ruled out; consider alternative therapy. Second and third trimesters: limited data; avoid unnecessary use. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to azelastine or any component of the formulation"]
| Precautions | ["Somnolence: may impair ability to drive or operate machinery; avoid alcohol or other CNS depressants.","Hepatic impairment: use with caution in patients with severe hepatic disease.","Renal impairment: dose adjustment may be needed in severe renal insufficiency.","Pediatric use: safety and efficacy in children <6 months not established.","Elderly: increased risk of dizziness and sedation."] |
| Food/Dietary | No significant food interactions. Alcohol may increase CNS depression (drowsiness); avoid concurrent use. |
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| Fetal Monitoring | Monitor maternal for excessive sedation, dizziness, and intolerance to intranasal administration. Fetal monitoring: no specific recommendations; however, if used chronically, consider periodic ultrasound for growth parameters if there is concern for maternal health compromise. |
| Fertility Effects | No human data on fertility. In animal studies, no impairment of fertility was observed in rats at oral doses up to 30 mg/kg/day. Theoretical risk due to anticholinergic effects (e.g., dry mucous membranes) may not affect fertility. Reversible upon discontinuation. |
| Clinical Pearls |
| Azelastine hydrochloride is an intranasal antihistamine approved for seasonal allergic rhinitis in children aged 5 and older. Fast onset: improvement within 1-2 hours. Common side effect: bitter taste (dysgeusia); advise rinsing mouth after use. May cause drowsiness; caution with other CNS depressants. Not for acute symptoms; use regularly for best effect. |
| Patient Advice | Use exactly as prescribed; do not exceed recommended dose. · Prime the spray by pumping 4 times before first use or after 3 days of non-use. · Blow nose gently before each dose. Insert nozzle into nostril, aim away from septum, and spray. · After spraying, tilt head back briefly; do not sniff forcefully. · If you experience a bitter taste, rinse mouth with water or juice after use. · Avoid contact with eyes. If spray contacts eyes, rinse with water. · Do not share the bottle with others to prevent infection. · Common side effects include headache, nasal burning, or drowsiness; report severe symptoms. · Store at room temperature away from moisture and heat. |