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
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
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 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
● 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
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
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