Which antihistamines are recommended for allergic rhinitis (rhinorrhea, sneezing, itching, urticaria) in adults and children, what are the appropriate doses, and what safety considerations and indications for adding intranasal corticosteroids or leukotriene receptor antagonists?

Antihistamine Selection for Allergic Rhinitis

First-Line Antihistamine Recommendation

For adults and children ≥6 years with allergic rhinitis, second-generation oral antihistamines—specifically fexofenadine, loratadine, or desloratadine—are recommended as first-line therapy for sneezing, rhinorrhea, and itching, with fexofenadine being the preferred choice when sedation must be absolutely avoided. 1, 2

Recommended Second-Generation Antihistamines and Dosing

Non-Sedating Options (Preferred)

• Fexofenadine is the only truly non-sedating antihistamine, maintaining this profile even at doses exceeding FDA recommendations, making it the gold standard when sedation avoidance is critical 2

  • Adults and children ≥12 years: 60 mg twice daily or 180 mg once daily 3
  • Children 6-11 years: 30 mg twice daily 3
  • No dose adjustment needed in renal impairment 2

• Loratadine does not cause sedation at recommended doses but may produce drowsiness when doses exceed recommendations or in patients with low body mass 1, 2

  • Adults and children ≥6 years: 10 mg once daily 2
  • Elderly ≥77 years: Consider 5 mg daily 2

• Desloratadine (active metabolite of loratadine) shares loratadine's non-sedating profile at recommended doses 1, 2

  • Adults and children ≥12 years: 5 mg once daily 2

Minimally Sedating Options (Second-Line)

• Cetirizine causes mild drowsiness in 13.7% of patients (vs 6.3% placebo) and can impair performance even when patients don't feel drowsy 1, 2, 4

  • Adults and children ≥6 years: 10 mg once daily 4
  • Requires 50% dose reduction in moderate renal impairment (CrCl 10-20 mL/min); avoid in severe renal impairment (CrCl <10 mL/min) 4

• Levocetirizine (active enantiomer of cetirizine) has similar sedation profile to cetirizine 2, 4

  • Adults and children ≥12 years: 5 mg once daily 4
  • Same renal dosing adjustments as cetirizine 4

Critical Safety Considerations

Avoid First-Generation Antihistamines

First-generation antihistamines (diphenhydramine, chlorpheniramine, brompheniramine) should be avoided due to significant sedation, performance impairment, and anticholinergic effects that patients may not subjectively perceive. 1, 2

• These agents increase risk of falls, fractures, subdural hematomas, and cognitive impairment, especially in elderly patients 1, 2
• Between 1969-2006,69 pediatric fatalities were associated with first-generation antihistamines in OTC preparations, with 41 deaths occurring in children <2 years 1
• FDA advisory committees recommended against OTC cough/cold medications containing first-generation antihistamines in children <6 years 1

Special Populations

• Children: Second-generation antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) have excellent safety profiles in children ≥6 years and should be used instead of first-generation agents to avoid impaired school performance 1, 2

• Elderly: Fexofenadine is preferred due to zero sedation risk and no anticholinergic effects; first-generation antihistamines are explicitly contraindicated by the American Geriatrics Society 2

• Pregnancy: All antihistamines should ideally be avoided, especially in the first trimester; if necessary, chlorpheniramine is often chosen due to long safety record, though it carries sedation risk 2, 4

• Renal impairment: Fexofenadine requires no dose adjustment; cetirizine and levocetirizine require 50% dose reduction in moderate impairment and should be avoided in severe impairment 2, 4

Symptom-Specific Efficacy

• Effective symptoms: All second-generation antihistamines effectively reduce sneezing, rhinorrhea, itching, and ocular symptoms 1, 5

• Limited efficacy: Oral antihistamines have minimal objective effect on nasal congestion—this is a critical limitation across all oral antihistamines 1, 2

• For urticaria: Antihistamines effectively relieve itching and reduce wheals; fexofenadine is FDA-approved for chronic idiopathic urticaria 3, 6

When to Add Intranasal Corticosteroids

Intranasal corticosteroids are the most effective monotherapy for allergic rhinitis and should be added or used as first-line therapy in the following situations: 1

• Moderate-to-severe persistent allergic rhinitis (symptoms >4 days/week and >4 weeks/year) 1, 5
• Nasal congestion is a prominent symptom, because oral antihistamines provide minimal relief of congestion 1, 2
• Inadequate response to antihistamine monotherapy after continuous use for 2-4 weeks 1
• Quality of life is significantly impaired by rhinitis symptoms 1

Intranasal Corticosteroid Options

• Fluticasone, mometasone, budesonide, and triamcinolone are all effective; no significant clinical differences exist between products despite differences in potency and binding affinity 1, 5
• Onset of action typically occurs within 12 hours, with some patients experiencing relief as early as 3-4 hours 1
• Intranasal corticosteroids are more effective than the combination of an oral antihistamine plus leukotriene receptor antagonist 1

When to Consider Leukotriene Receptor Antagonists

Leukotriene receptor antagonists (montelukast) are less effective than intranasal corticosteroids and have no significant efficacy advantage over oral antihistamines, but may be considered in specific situations: 1

• Patients with both allergic rhinitis and asthma, as montelukast is approved for both conditions 1
• Patients unresponsive to or noncompliant with intranasal corticosteroids 1
• Combination therapy with an antihistamine when intranasal corticosteroids fail or are not tolerated 1

Intranasal Antihistamines as Alternative

• Azelastine and olopatadine (intranasal antihistamines) have rapid onset of action and are equal or superior in efficacy to oral second-generation antihistamines 1, 5
• They provide clinically significant relief of nasal congestion, unlike oral antihistamines 1
• Side effects: Bitter taste and somnolence with azelastine; more frequent dosing required 1
• Appropriate for episodic or as-needed use due to rapid onset 1

Clinical Decision Algorithm

1. Mild intermittent symptoms (sneezing, itching, rhinorrhea): Start oral second-generation antihistamine (fexofenadine, loratadine, or desloratadine) 1, 5

2. Moderate-to-severe or persistent symptoms: Start intranasal corticosteroid as monotherapy or add to existing antihistamine 1, 5

3. Prominent nasal congestion: Use intranasal corticosteroid ± oral antihistamine; oral antihistamine alone is insufficient 1, 2

4. Coexisting asthma: Consider intranasal corticosteroid plus leukotriene receptor antagonist, or levocetirizine which has evidence for both upper and lower respiratory symptoms 1, 4

5. Sedation must be avoided (drivers, machinery operators, fall-risk patients): Use fexofenadine exclusively 2

6. Renal impairment: Use fexofenadine (no adjustment needed) or adjust cetirizine/levocetirizine doses appropriately 2, 4

Common Pitfalls to Avoid

• Do not assume all second-generation antihistamines are equally non-sedating—cetirizine and levocetirizine carry meaningful sedation risk 1, 2
• Do not use oral antihistamines alone for nasal congestion—add intranasal corticosteroid instead of switching between antihistamines 1, 2
• Do not use first-generation antihistamines in elderly patients, children, or anyone requiring alertness—they significantly increase fall risk and impair cognition 1, 2
• Continuous daily use is more effective than as-needed use for seasonal or perennial allergic rhinitis due to ongoing allergen exposure 1, 2
• Performance impairment can occur without subjective drowsiness, particularly with cetirizine—counsel patients about driving and machinery operation 2, 4
• Do not prescribe standard doses of cetirizine or levocetirizine in renal impairment without dose adjustment—both require 50% reduction in moderate impairment 4