Intranasal Corticosteroids (INCSs)

Overview

Mechanism of Action

• Suppress activation of inflammatory cells: mast cells, eosinophils, and basophils
• Increase local concentrations of active steroid while limiting systemic absorption
• Reduce naso-ocular reflex, accounting for their benefit on ocular symptoms as well

Available Agents

• K.J. Lee's Essential Otolaryngology

Indications

1. Allergic rhinitis (AR) - preferred for perennial and moderate-to-severe seasonal AR
2. Non-allergic rhinitis (NAR) - beclomethasone propionate and fluticasone propionate are the only FDA-approved agents specifically for NAR
3. NARES (non-allergic rhinitis with eosinophilia syndrome) - mainstay of treatment
4. Chronic rhinosinusitis - used as adjunctive medical therapy
5. Nasal polyps - mometasone and fluticasone furoate have specific labeling
6. Rhinitis in pregnancy - budesonide preferred (Pregnancy Category B)

Dosing Principles

• Daily dosing is more efficacious than as-needed dosing
• Onset of action: 3-5 hours after first dose, with full effect up to 60 hours; some newer agents within 12 hours
• For seasonal allergies, should be started 2 weeks prior to pollen season
• Evidence that dual therapy (INCS + antihistamine) is superior to INCS monotherapy is lacking
• When adding an antihistamine to an INCS, an intranasal antihistamine (azelastine, olopatadine) is preferred over an oral one

Place in Therapy - ARIA Algorithm

Side Effects

• Local: Epistaxis, nasal dryness, throat dryness, local irritation, headaches
• Rare: Nasal septal perforation (especially with incorrect technique aimed at the septum)
• Technique: Aim the spray away from the nasal septum to reduce epistaxis risk
• Ocular: No clinically relevant impact on intraocular pressure, glaucoma, lens opacity, or cataract formation
• Growth in children: May have a negative effect on short-term growth in children - use the lowest effective dose

Systemic Safety & HPA Axis

• Newer agents (mometasone, fluticasone, ciclesonide, fluticasone furoate) have minimal systemic bioavailability and are free of clinically significant HPA axis suppression
• Older agents (beclomethasone, flunisolide) have higher bioavailability and greater systemic effects
• Budesonide is safe in pregnancy (Category B) but still aim for lowest effective dose

Comparison with Other Rhinitis Drugs

Recent Evidence (2024-2026)

Antihistamines in ENT

Classification

First-Generation (Sedating) Antihistamines

Second-Generation (Non-Sedating) Antihistamines

• K.J. Lee's Essential Otolaryngology

Intranasal (Topical) Antihistamines

• Azelastine is as effective as or superior to oral antihistamines for nasal congestion
• Intranasal antihistamines are at least as effective as intranasal corticosteroids for sneezing, itching, rhinorrhea, and ocular symptoms
• Recommendation: Not as monotherapy but combined with intranasal corticosteroids (the most effective combination for allergic rhinitis)

Mechanism of Action

• Competitively block histamine H1 receptors on target tissues
• Reduce histamine-mediated effects: vasodilation, vascular permeability, mucus secretion, itch, and smooth muscle contraction
• Azelastine also has additional anti-inflammatory effects:
  • Inhibits synthesis of leukotrienes, kinins, and cytokines
  • Prevents generation of superoxide free radicals
  • May modulate TRPV1 ion channel activity (explaining efficacy in non-allergic rhinitis)
• Cummings Otolaryngology

Indications in ENT

1. Allergic Rhinitis (AR) - PRIMARY INDICATION

• Oral long-acting H1 antihistamines (fexofenadine, loratadine, desloratadine, cetirizine, levocetirizine) are effective for:
  • Nasopharyngeal itching, sneezing, and watery rhinorrhea
  • Ocular symptoms (itching, tearing, erythema)
  • Reduce nasal and ocular symptoms by ~30-35%
• Less efficacious for nasal congestion (this is better handled by INCSs or decongestants)
• Preferred for seasonal, mild disease; intranasal corticosteroids are preferred for perennial, severe disease
• Antihistamines may become ineffective with continuous allergen exposure (perennial AR, peak season) - may be little better than placebo in those settings
• When adding antihistamine to INCS, intranasal antihistamine is preferred over oral
• Harrison's Principles of Internal Medicine 22E; Goldman-Cecil Medicine

2. Non-Allergic Rhinitis (NAR)

• Intranasal azelastine and olopatadine are effective for vasomotor rhinitis (VMR) and non-NARES subtypes
• Oral antihistamines have a limited role in NAR but may benefit patients with the NARES subtype who have sneezing and itching as dominant symptoms
• Azelastine's TRPV1 modulation may explain its efficacy even in non-inflammatory NAR subtypes
• Side effect to note: azelastine has a persistent bitter taste (can be masked with sucralose)
• Olopatadine not FDA-approved for NAR but has demonstrated efficacy

3. Allergic Conjunctivitis (associated with AR)

• Topical antihistamines (olopatadine, azelastine, ketotifen, epinastine) administered to the eye are more effective than oral antihistamines for rapid relief of itching and redness
• Topical antihistamine + mast cell stabilizer combinations (dual-action agents: azelastine, ketotifen, olopatadine) are often very effective for exacerbations
• Topical antihistamine-decongestant combinations (naphazoline + antazoline; naphazoline + pheniramine) are available OTC

4. Vestibular Disorders / Vertigo

• Antihistamines are vestibulosuppressants - decrease excitability of the labyrinth
• Used in Meniere's disease and other causes of peripheral vertigo
• First-generation agents (meclizine, promethazine) are used for this indication due to their anticholinergic and sedating properties
• Cyclizine: used for motion sickness, nausea/vomiting, and vertigo
• Ganong's Review of Medical Physiology; Bradley & Daroff's Neurology

5. Urticaria and Angioedema (may present to ENT with laryngeal/pharyngeal angioedema)

• Second-generation antihistamines (cetirizine 10 mg, levocetirizine 5 mg, fexofenadine 180 mg, loratadine 10 mg) are first-line for acute urticaria
• For chronic urticaria: start with second-generation antihistamine once daily; advance dose up to 4× daily at 2-4 week intervals if needed
• First-generation hydroxyzine may be added as an evening dose in refractory cases

6. Post-Nasal Drip and Cough

• First-generation antihistamines are used for cough caused by post-nasal drip/direct nasal irritation
• Sequential treatment for chronic cough includes oral first-generation antihistamine + decongestant ± intranasal steroid

7. Upper Respiratory Tract Infections

• Antihistamines do not reduce complications such as otitis media in children with URTIs
• They do not benefit rhinorrhea or cough in children with common colds (note for pediatric ENT practice)

Comparison: Oral vs. Intranasal vs. Topical Ocular

Side Effects Summary

Recent Evidence (2024-2026)