Can we give Levocetrizine (antihistamine) plus Montelukast (leukotriene receptor antagonist) to patients with allergic rhinitis or asthma?

Can Levocetirizine Plus Montelukast Be Given to Patients with Allergic Rhinitis or Asthma?

Yes, the combination of levocetirizine and montelukast can be given to patients with allergic rhinitis or asthma, but this combination should be reserved as alternative therapy for patients who are unresponsive to or not compliant with intranasal corticosteroids, which remain the most effective first-line treatment. 1

Treatment Hierarchy for Allergic Rhinitis

First-Line Therapy

• Intranasal corticosteroids are the most effective treatment for allergic rhinitis and should be tried first 1
• Intranasal corticosteroids are superior to the combination of antihistamine plus leukotriene receptor antagonist (LTRA) in most studies 1

When to Consider Levocetirizine Plus Montelukast

• This combination provides an alternative for patients who are unresponsive to or not compliant with intranasal corticosteroids 1
• The concomitant use of an antihistamine and LTRA may have an additive effect, though not all studies have shown this benefit 1
• There is no significant difference in efficacy between LTRA and antihistamines when used alone, but their combination may be additive 1

Special Populations Where Combination Therapy Is Particularly Useful

Patients with Coexisting Asthma and Allergic Rhinitis

• As many as 40% of patients with allergic rhinitis have coexisting asthma, making montelukast particularly attractive since it treats both conditions 1
• The combination of montelukast and a second-generation antihistamine may protect against seasonal decrease in lung function in patients with allergic rhinitis 1
• Recent evidence from a 2025 meta-analysis demonstrates that montelukast combined with levocetirizine significantly improves nasal symptoms in patients with allergic rhinitis and asthma (SMD of NSS: -2.56,95%CI: -2.77 to -2.35) 2
• A large prospective study of 2,254 patients showed significant improvement in total nasal symptom scores and quality of life at 3 and 6 months with the combination, with minimal adverse effects 3

Pediatric Considerations

• Montelukast has an excellent safety profile and is approved down to 6 months of age for perennial allergic rhinitis 1
• In children with mild persistent asthma and coexisting allergic rhinitis, montelukast may be considered for monotherapy 1
• This combination is particularly attractive when treating children whose parents are steroid-phobic 1

Evidence for Efficacy

Comparative Effectiveness

• The combination shows gradual improvement over 6 weeks of treatment, with significant enhancement compared to first-day therapy 4
• Both montelukast and levocetirizine alone, as well as their combination, significantly improve nasal symptoms during the first 24 hours 4
• However, one study found no additional benefit of combination therapy over monotherapy for symptom control, suggesting montelukast alone may be cost-effective 5

Onset and Duration of Action

• Montelukast has an onset of action by the second day of daily treatment 1
• Improvement gradually increases during 6 weeks of treatment, especially with combination therapy 4

Important Safety Considerations and Pitfalls

Neuropsychiatric Events

• Neuropsychiatric events have been reported with leukotriene antagonists, though evidence of causation is conflicting 6, 7
• The FDA has added warning labeling regarding these potential adverse effects 6

Common Pitfalls to Avoid

• Do not bypass intranasal corticosteroids - they are superior to the combination and should be tried first 6, 7
• Do not use this combination for non-allergic rhinitis, where it is not indicated 7
• Never use montelukast as monotherapy for asthma - it should only be used in combination with inhaled corticosteroids for persistent asthma 1

Clinical Algorithm for Decision-Making

1. Start with intranasal corticosteroids for allergic rhinitis 1
2. If inadequate response, non-compliance, or contraindication to intranasal corticosteroids exists, consider levocetirizine plus montelukast combination 1
3. For patients with both allergic rhinitis and asthma, strongly consider this combination as it addresses both upper and lower airway disease 1, 7
4. Monitor for neuropsychiatric symptoms, particularly in children and adolescents 6
5. Assess response at 2 days (initial), 3 weeks, and 6 weeks for optimal benefit 1, 4

Cost-Effectiveness

• The combination of montelukast-levocetirizine demonstrates better cost-effectiveness compared to montelukast-fexofenadine 8
• Some evidence suggests montelukast alone may be most cost-effective if equally effective 5