Montelukast and Levocetirizine in Allergic Rhinitis – An Evidence-based Approach

Allergic rhinitis is one of the most common allergic diseases worldwide, affecting about 10-25% of the global population. It continues to be one of the top ten reasons for a visit to a primary care physician.

In India, the burden of allergic rhinitis has seen an exponential rise over the past few decades. The current estimates suggest that at least 20-30% population in India suffers from allergic rhinitis.1

A Clinician’s Approach to Allergic Rhinitis

Allergic rhinitis (AR) is an atopic disease characterized by an early IgE-mediated immune response to inhaled antigens and a subsequent leukotriene-mediated delayed response. Pathogenesis in allergic rhinitis has distinct clinical stages viz. allergen sensitization, re-exposure to allergens, followed by the development of early and late-phase reactions and nasal symptoms. The most classical presentation is with symptoms like sneezing, nasal congestion, clear rhinorrhea, and nasal pruritus.2

Schematic representation of the natural course in allergic rhinitis

The diagnosis of allergic rhinitis is often made clinically based on the characteristic history, presentation and good response to empirical therapy. Allergen-specific IgE testing may be performed for morespecificity. Management options consist of allergen avoidance, agents that provide symptomatic relief,anti-inflammatory therapies and allergen-specific immunological therapies. Antihistamines, glucocorticoids and leukotriene receptor antagonists form the cornerstone of pharmacotherapy forallergic rhinitis. Recent advances in therapy include intranasal antihistamines and novel methods of delivery for intranasal steroids.

Montelukast and Levocetirizine Combination For Allergic Rhinitis

Montelukast is an orally active, highly selective cysteinyl leukotriene type-1 receptor antagonist, whereas Levocetirizine is a potent second-generation histamine receptor antagonist. Together, the combination can effectively combat both early and late-phase immune reactions that form the underlying pathophysiology of allergic rhinitis.4

Montelukast + Levocetirizine FDC vs Individual Montelukast/Levocetirizine

● In a double-blind, randomized, parallel-group, comparative study, 274 patients of allergic rhinitis were divided into groups to receive either Montelukast or Levocetirizine alone; or a fixed-dose combination of the two molecules for a 14 days treatment period. The mean daytime and nightime nasal symptoms scores were found to be significantly better for the fixed-dose combination of Montelukast and Levocetirizine as compared to either agent alone.5
● A 4-week, randomized, multicenter, double-blind, Phase III trial evaluated the efficacy of Montelukast alone vs FDC of Montelukast+Levocetirizine in 228 patients with allergic rhinitis and concomitant asthma. The Montelukast/Levocetirizine group reported significant reductions in mean daytime nasal symptom score and superior results in other efficacy parameters vs Montelukast alone.6

Montelukast + Levocetirizine FDC vs Other Agents

An open-label, randomized, prospective, and parallel-group study compared the efficacy of Montelukast+Levocetirizine FDC with Montelukast+Fexofenadine for the treatment of allergic rhinitis.
Both groups showed significant improvement as compared to baseline in terms of reduction in the total nasal symptoms scores, but patients in the Montelukast+Levocetirizine group had a comparativelybetter quality of life, lesser side effects and low cost of therapy.7

Montelukast+Levocetirizine - Looking Beyond Allergic Rhinitis?

The combination of Montelukast and Levocetirizine exhibits remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins,
cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19.

A pilot study in Massachusetis administered Montelukast+Levocetirizine
combination to COVID-19 patients in addition to the existing treatment protocols. No intubations or deaths were found in this cohort of patients treated with the Montelukast+Levocetirizine combination. There is also
data to suggest that combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost-effectively reducing both
morbidity and mortality. Currently, trials are underway to further analyze the safety and efficacy of this combination in the COVID-19 therapy.8

In a nutshell, the combination of second-generation antihistamine drugs like Levocetirizine and leukotriene type-1 receptor antagonist drugs like Montelukast make a formidable combination to treat allergic rhinitis spectrum. They may also potentially have a place in therapy for other respiratory conditions like COVID-19.


1. Chandrika D. Allergic rhinitis in India: an overview. Int J Otorhinolaryngol Head Neck Surg 2017;3:1-6.
2. Wheatley LM, Togias A. Clinical practice. Allergic rhinitis. N Engl J Med. 2015 Jan 29;372(5):456-63.
3. Oates, John A.; Wood, Alastair J.J.; Naclerio, Robert M. (1991). Allergic Rhinitis. New England Journal of Medicine, 325(12), 860–869. doi:10.1056/NEJM199109193251206
4. Kim MK et al.. A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis. Clin Ther. 2018 Jul;40(7):1096-1107.e1
5. Bylappa, Kiran & Silvia Cr, Wilma. (2018). Evaluation of efficacy of fixed dose combination of montelukast and levocetirizine compared to monotherapy of montelukast and  levocetirizine in patients with seasonal allergic rhinitis. International Journal of Otorhinolaryngology and Head and Neck Surgery. 4. 467. 10.18203/issn.2454-5929.ijohns20180708.
6. Kim MK, Lee SY, Park HS, Yoon HJ, Kim SH, Cho YJ, Yoo KH, Lee SK, Kim HK, Park JW, Park HW, Chung JH, Choi BW, Lee BJ, Chang YS, Jo EJ, Lee SY, Cho YS, Jee YK, Lee JM, Jung J, Park CS. A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis. Clin Ther. 2018 Jul;40(7):1096-1107.e1.
7. S, Sharma DK, Kaur G, Singh A, Bhagat S, Matreja PS. Comparison of safety, effectiveness and cost-effectivenes.s of Combination of Levocetirizine and Fexofenadine with Montelukast in Allergic Rhinitis and its effect on quality of life. Int Arch BioMed Clin Res [Internet]. 2020Jun.29
8. May BC, Gallivan KH. Levocetirizine and montelukast in the COVID-19 treatment paradigm. Int Immunopharmacol. 2022 Feb;103:108412