Can you take montelukast and Zyrtec (cetirizine) together?

Can You Take Montelukast and Zyrtec Together?

Yes, you can safely take montelukast and Zyrtec (cetirizine) together, and this combination is actually more effective than either medication alone for treating allergic rhinitis. 1

Evidence Supporting Combination Therapy

The combination of a leukotriene receptor antagonist (montelukast) and an antihistamine (like cetirizine, which is similar to Zyrtec) provides superior symptom control compared to monotherapy:

• Guideline-endorsed approach: Major allergy guidelines explicitly state that "the combination of an antihistamine and LTRAs is superior to either therapy when given alone" for allergic rhinitis treatment. 1

• Complementary mechanisms: These medications work through different pathways—montelukast blocks inflammatory leukotrienes while antihistamines block histamine receptors—providing additive therapeutic benefit. 1

• Recent high-quality evidence: A 2025 systematic review and meta-analysis demonstrated that montelukast combined with levocetirizine (a closely related antihistamine to cetirizine) significantly improved nasal symptom scores (SMD of -2.56) compared to monotherapy, with good safety profiles. 2

Clinical Scenarios Where This Combination Is Particularly Useful

For allergic rhinitis patients inadequately controlled on single therapy:

• When intranasal corticosteroids are refused, not tolerated, or contraindicated, the antihistamine-montelukast combination provides an effective oral alternative. 1
• This combination may be as effective as corticosteroid use in some patients with seasonal allergic rhinitis. 1

For patients with both allergic rhinitis and asthma:

• Montelukast treats both upper and lower airway inflammation simultaneously, making it particularly valuable when combined with an antihistamine for comprehensive symptom control. 1
• A 2018 Phase III trial showed the montelukast/levocetirizine combination significantly reduced daytime nasal symptoms (P = 0.045) in patients with perennial allergic rhinitis and mild-to-moderate asthma. 3
• The combination may provide better protection against seasonal decreases in lung function. 1

Safety Profile

Both medications are well-tolerated with minimal drug interactions:

• Montelukast has an excellent safety profile and is approved for use in children as young as 6 months for perennial allergic rhinitis. 1
• Second-generation antihistamines like cetirizine have negligible sedative effects and excellent tolerability. 4
• Adverse events occur at similar frequencies whether taking montelukast, antihistamines, or their combination compared to placebo. 5

Important Caveats

This combination has limitations:

• While effective, the antihistamine-montelukast combination is generally less effective than intranasal corticosteroids as monotherapy for allergic rhinitis. 1
• Neither medication provides rapid relief for acute symptoms—montelukast has a delayed onset of action (effective by the second day), making it unsuitable for immediate symptom control. 1, 6
• For non-allergic conditions like isolated dry cough, this combination is not first-line therapy. 6

Cost considerations:

• The montelukast-cetirizine combination is cost-effective, with better cost-effectiveness ratios than some alternative antihistamine combinations. 7