AZELASTINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZELASTINE HYDROCHLORIDE (AZELASTINE HYDROCHLORIDE).
Azelastine hydrochloride is a phthalazinone derivative that exerts its effect by competitively inhibiting histamine at the H1 receptor site. It also stabilizes mast cells, reducing the release of inflammatory mediators such as histamine, leukotrienes, and cytokines. This dual action provides both antihistaminic and anti-inflammatory effects.
| Metabolism | Azelastine is primarily metabolized in the liver via cytochrome P450 enzymes, specifically CYP3A4 and CYP2D6, to its major active metabolite, desmethylazelastine. It undergoes oxidative metabolism, with less than 10% excreted unchanged in urine. |
| Excretion | Approximately 75% of the dose is excreted in feces as unchanged drug and metabolites; about 25% is excreted renally, with less than 10% as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 22 hours (range 20–25 hours) following oral administration, supporting twice-daily dosing. For ophthalmic and intranasal routes, systemic half-life is similar due to absorption. |
| Protein binding | Approximately 88% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 14.5 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Intranasal: systemic bioavailability is about 40% of the administered dose due to absorption; ophthalmic: negligible systemic absorption (<0.1%); oral: absolute bioavailability is approximately 68% due to first-pass metabolism. |
| Onset of Action | Intranasal: clinical effect (relief of nasal symptoms) begins within 1–3 hours; ophthalmic: relief of ocular itching occurs within 3 minutes; oral: onset of antihistamine effect is within 1 hour. |
| Duration of Action | Intranasal: duration of action is up to 12 hours, consistent with twice-daily dosing; ophthalmic: symptom relief lasts at least 8 hours after a single dose; oral: duration of antihistamine effect is approximately 24 hours. |
1 spray (137 mcg) per nostril twice daily; ophthalmic: 1 drop in affected eye(s) twice daily.
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (CrCl <15 mL/min). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Intranasal: 1 spray per nostril twice daily for ages >6 years; ophthalmic: 1 drop twice daily for ages >3 years; no weight-based dosing needed. |
| Geriatric use | No specific dose adjustment; monitor for sedation and dizziness due to potential increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZELASTINE HYDROCHLORIDE (AZELASTINE HYDROCHLORIDE).
| Breastfeeding | It is not known whether azelastine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azelastine is administered to a nursing woman. The M/P ratio is unknown. |
| Teratogenic Risk | Azelastine hydrochloride is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, azelastine was not teratogenic in rats, mice, or rabbits at doses up to 6.5, 9.0, and 28.5 times the maximum recommended human daily intranasal dose, respectively. However, increased fetal mortality, reduced fetal weight, and skeletal variations were observed in rats at a maternally toxic dose. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Bitter taste Nasal irritation |
| Serious Effects |
["Known hypersensitivity to azelastine or any component of the formulation.","Avoid use in patients with severe hepatic impairment (Child-Pugh class C) due to lack of safety data."]
| Precautions | ["Somnolence: May cause drowsiness; patients should avoid driving or operating machinery until tolerance is established.","Nasal irritation: Epistaxis, nasal ulceration, and nasal burning may occur with intranasal use.","Ocular irritation: Transient burning or stinging with ophthalmic solution.","Avoid concomitant use with alcohol or other CNS depressants due to additive effects.","Use with caution in patients with hepatic impairment (Child-Pugh class B or C)."] |
| Food/Dietary |
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| Fetal Monitoring | No specific maternal or fetal monitoring is routinely recommended beyond standard obstetric care. However, due to potential anticholinergic effects, monitor for maternal sedation, dizziness, and nasal irritation. |
| Fertility Effects | In animal studies, azelastine administered orally at doses up to 28.5 times the maximum recommended human daily intranasal dose did not impair fertility in rats. No human data on fertility effects are available. |
| No specific food interactions. Avoid alcohol as it may increase drowsiness. Grapefruit juice has no known interaction. |
| Clinical Pearls | For allergic rhinitis, onset of action is within 3 hours; for conjunctivitis, within minutes. Bitter taste (dysgeusia) is common with intranasal use; advise patients to avoid tilting head back after administration. Systemic absorption is minimal. Can be used concurrently with intranasal corticosteroids for additive effect. Limited data in pregnancy; consider risk-benefit. |
| Patient Advice | For nasal spray: blow nose gently before use; insert nozzle into nostril and spray while breathing in through nose; do not tilt head back after spraying. · For eye drops: wash hands before use; tilt head back, pull lower eyelid down, and apply one drop; close eyes for 1-2 minutes; avoid touching dropper tip to eye or any surface. · Common side effect: bitter taste in mouth (usually temporary); do not swallow the nasal spray. · Use consistently for best results; may take several days for full effect. · Do not use beyond expiration date; discard 1 month after opening eye drops. · If using other eye medications, wait at least 5 minutes between applications. |