Generic Name

Azelastine

Mechanism

Azelastine is a highly selective, competitive antagonist of the histamine H₁ receptor located on nasal mucosal cells, vascular endothelium, and sensory nerve endings.
• Inhibition of histamine release prevents the cascade that leads to vasodilation, increased vascular permeability, and sensory nerve stimulation.
• By blocking peripheral H₁ receptors, it reduces the symptoms of allergic rhinitis—nasal congestion, rhinorrhea, pruritus, and sneezing—without significant central nervous system penetration.
• Because of its rapid onset (~10 min), it is especially useful for acute management of allergic symptoms.

Pharmacokinetics

• Formulation: 0.1 % nasal spray (1 mg per vial, 0.05 mg per spray) or 0.5 % ocular drops.
• Absorption: Minimal systemic absorption from the nasal mucosa (≤ 2 % of a single spray).
• Distribution: Primarily confined to the upper respiratory tract; plasma concentrations are ≤ 0.02 µg/mL.
• Metabolism: Hepatic via CYP3A4 and CYP1A2, yielding inactive metabolites.
• Elimination: Renal excretion (~30 %) and fecal (~10 %) routes.
• Half‑life: 5–6 h (with rapid decline in nasal mucosal concentration).
• Special populations: Azelastine is safe in hepatic impairment except severe cirrhosis; caution in severe renal dysfunction as clearance may be reduced.

Indications

• Allergic rhinitis (seasonal or perennial) – nasal spray 1–2 sprays/nostril twice daily.
• Allergic conjunctivitis – ocular drops 1–2 drops per eye twice daily.
• Post‑nasal drip and nasal itch – useful as adjunct to intranasal steroids when monotherapy is insufficient.

Contraindications

• Hypersensitivity to azelastine, sulfites, or any excipients.
• Severe hepatic impairment (Child‑Pugh class C).
• Pregnancy: Category B; limited evidence of fetal risk; use only if benefit outweighs risk.
• Lactation: No significant transfer into breast milk; may be considered if clinically required.
• Warfarin interaction: No significant effect, but monitor INR if concomitant use of anticoagulants.
• CNS depression: Although uncommon, azelastine may potentiate sedative CNS agents (e.g., benzodiazepines, alcohol).
• Cardiac arrhythmias: May prolong QT interval when used at excessive doses or with other QT‑prolonging drugs; avoid in patients with known conduction disorders.

Dosing

• First‑day dosing: Begin immediately for symptomatic relief; subsequent doses maintain control.
• Duration: Can be used continuously for chronic allergic rhinitis; withdrawal may result in recurrence of symptoms.

Adverse Effects

Common
• Nasal irritation or burning
• Headache
• Dysgeusia (taste alteration)
• Mild somnolence (rare)

Serious (rare)
• Anaphylaxis (e.g., urticaria, angioedema)
• Severe CNS depression when combined with alcohol or benzodiazepines
• QT‑interval prolongation (when combined with other QT‑prolonging agents)
• Hepatotoxicity (in patients with underlying liver disease)

Monitoring

• Symptom control: Assess nasal congestion, rhinorrhea, and sneezing scores at baseline and every 4 weeks.
• Adverse effects: Screen for sedation, headaches, or any allergic reaction during each visit.
• Liver function tests: Baseline AST/ALT, especially in patients with chronic liver disease; repeat if symptoms arise.
• Pregnancy status: Pregnant patients should be reevaluated each trimester.

Clinical Pearls

• Rapid onset: Nasal spray starts relieving symptoms within 10 minutes; useful for patients who need quick relief before activity.
• Adjunct to steroids: In patients who do not tolerate or inadequately respond to intranasal corticosteroids, azelastine can bridge the gap and reduce the steroid dose needed.
• Use “with caution” for the elderly: Older patients may be more susceptible to CNS depression; limit to 2 sprays per nostril if simultaneous use of sedatives.
• Cross‑reactivity: Patients with histamine intolerance or mast cell activation syndrome rarely benefit; consider alternative antihistamines.
• Potentiation of local anesthetics: When used with topical anesthetics (e.g., lidocaine) for nasal procedures, monitor for additive local effects.
• Avoid spray in children under 4 years: Not approved for this age group due to lack of safety data; ocular drops may be used under supervision.

Bottom line: Azelastine remains a cornerstone for the pharmacologic management of allergic rhinitis and conjunctivitis, offering rapid, targeted relief with minimal systemic exposure when administered appropriately.