Can You Take Cetirizine with Montelukast?
Yes, you can safely take cetirizine (an antihistamine) with montelukast (a leukotriene receptor antagonist), and this combination is specifically recommended by major allergy and asthma societies as alternative therapy for allergic rhinitis, particularly when you have both rhinitis and asthma together. 1
When This Combination Is Appropriate
The American Academy of Allergy, Asthma, and Immunology recommends this combination as alternative therapy after intranasal corticosteroids have failed or are not tolerated, as intranasal steroids remain superior first-line treatment. 1 However, this combination offers distinct advantages in specific clinical scenarios:
Primary Indications for Combination Therapy
For patients with both allergic rhinitis and asthma, the combination addresses both upper and lower airway disease simultaneously, which is a key advantage over treating each condition separately. 1
The combination of antihistamine and leukotriene antagonist produces predominant inhibition of allergen-induced allergy and late-phase airway obstruction in asthmatics, making it particularly effective for dual airway disease. 2
Several controlled studies demonstrate that combination therapy with antihistamines and antileukotrienes may be as effective as corticosteroid use in patients with allergic asthma and seasonal allergic rhinitis. 2
Evidence Supporting the Combination
A 2025 meta-analysis covering 2,950 patients showed that montelukast combined with levocetirizine (a closely related antihistamine to cetirizine) significantly improved nasal symptoms with a pooled effect size of -1.28, and was more effective than monotherapy. 3
A randomized Phase III trial demonstrated that the fixed-dose combination significantly reduced daytime nasal symptom scores compared to montelukast alone (P = 0.045), while maintaining similar safety profiles. 4
The use of montelukast in combination with antihistamines such as cetirizine has generally resulted in greater efficacy than when these agents were used alone, and in some studies has produced results comparable with intranasal corticosteroids. 5
Treatment Algorithm
Step 1: First-Line Therapy
- Start with intranasal corticosteroids as monotherapy for allergic rhinitis, as they are the most effective medication class for controlling symptoms. 1
Step 2: When to Add or Switch to Combination
If intranasal corticosteroids fail, are not tolerated, or the patient refuses nasal administration, then the cetirizine-montelukast combination becomes appropriate. 1
For patients with concurrent allergic rhinitis and asthma, consider the combination earlier in the treatment algorithm, as it treats both conditions simultaneously. 1
Step 3: Special Populations
- For preschool children with persistent allergic rhinitis, montelukast can be considered as monotherapy, though the combination with antihistamines may provide additional benefit. 1
Safety Considerations and Important Caveats
Neuropsychiatric Risks with Montelukast
The American Academy of Allergy, Asthma, and Immunology recommends carefully evaluating risks versus benefits before initiating montelukast, particularly given that alternative therapies (intranasal corticosteroids) are more effective and lack serious psychiatric risks. 6
Monitor patients for mood changes, behavioral changes, or suicidal ideation when using leukotriene antagonists, and patients with current or prior psychiatric illness require particularly close monitoring. 6
Treatment with montelukast should be stopped immediately upon occurrence of any neuropsychiatric side effects—there is no role for continued monitoring while symptomatic. 6
Sedation Profile
- Cetirizine (a second-generation antihistamine) has a lower sedation risk compared to first-generation antihistamines, making it preferable for daytime use. 1
Common Pitfalls to Avoid
Do not prescribe montelukast as first-line for isolated allergic rhinitis without asthma, as this violates guideline recommendations and exposes patients to unnecessary psychiatric risk when more effective alternatives exist. 6
Do not use this combination for non-allergic upper airway cough syndrome, as it is not indicated for non-allergic conditions. 1
Avoid using montelukast as monotherapy for moderate-severe asthma control, as it should not replace inhaled corticosteroids in these patients. 1
Bottom Line for Clinical Practice
The cetirizine-montelukast combination is safe and effective, particularly valuable for patients with both allergic rhinitis and asthma who have failed or cannot tolerate intranasal corticosteroids. 1 The combination provides dual-pathway inhibition of allergic inflammation and has demonstrated superior efficacy compared to monotherapy in controlled trials. 3, 4 However, always counsel patients about potential neuropsychiatric effects of montelukast and maintain intranasal corticosteroids as your first-line approach when possible. 6