Allergic rhinitis stands as the most prevalent allergic condition globally, affecting approximately 18% to 40% of the general population. While anti-allergic medications, including certain antihistamines, offer relief, they often come with adverse effects such as drowsiness, further compromising quality of life. 

Allergic rhinitis stands as the most prevalent allergic condition globally, affecting approximately 18% to 40% of  the general population.

While anti-allergic medications, including certain antihistamines, offer relief, they often come with adverse effects such as drowsiness, further compromising quality of life. Addressing allergic rhinitis (AR) remains a formidable task in global healthcare, with existing treatments offering limited relief from its burdensome symptoms. Despite decades of available options, patients still struggle with compromised quality of life due to persistent symptoms. 

AR stems from exposure to allergens like pollen, mites, and animal dander, triggering a cascade of immune responses in susceptible individuals. This includes the activation of specific immunoglobulin E (IgE) receptors on mast cells and basophils, leading to early and late-phase reactions characterized by various inflammatory processes. The resulting nasal and ocular symptoms significantly impair daily functioning and quality of life. 

Present pharmacological landscape 

Current pharmacological management relies on symptomatic relief through antihistamines, corticosteroids, nasal decongestants, and leukotriene receptor antagonists. Traditional antihistamines have fallen out of favour due to side effects, paving the way for newer-generation options like desloratadine and levocetirizine, which offer improved safety profiles. Intranasal formulations provide targeted relief, while corticosteroids serve as primary therapy by suppressing immune responses. Combination therapies, such as intranasal antihistamines with corticosteroids, have shown superior efficacy. 

Montelukast, a leukotriene receptor antagonist, stands out for its efficacy in reducing night-time symptoms, particularly when combined with H1 antihistamines. While nasal decongestants alleviate congestion, their overuse can lead to rebound symptoms. 

Innovative Combination Therapy Recent studies explore the efficacy of combining montelukast and levocetirizine, offering a promising approach to AR management. Panchal et al (2021) conducted a Phase III trial, demonstrating the superior efficacy of this combination over monotherapy in seasonal allergic rhinitis (SAR) patients. The fixed-dose combination (FDC) significantly improved daytime nasal symptoms, night-time symptoms, and overall quality of life, with favourable safety profiles. 

Mahatme et al (2016) compared montelukast-levocetirizine with montelukast-fexofenadine combinations, highlighting the former's cost-effectiveness alongside significant symptom reduction. 

Bilayer technology 

Similarly, Rathod et al found that combining montelukast with levocetirizine presents notable advantages over individual drug administration, particularly for patients experiencing persistent allergic rhinitis-related impairment. 

Montelukast sodium, being alkaline and stable, and levocetirizine dihydrochloride, possessing acid stability, present a formulation challenge when combined in a matrix tablet. Their interaction may render the formulation unstable over its shelf life. Thus, a bilayer tablet is recommended to enhance stability. This bilayer configuration ensures prolonged stability of both drugs in combination, surpassing the performance of matrix tablets in stability studies. 

Quality of life 

Ciebiada et al conducted a study to evaluate the impact of treating persistent allergic rhinitis using montelukast, desloratadine, and levocetirizine either individually or in combination on quality of life. 

Methodology: The study, spanning 32 weeks, employed a randomised, double-blind, placebo-controlled crossover design with two arms. In one arm, 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo, while in the other arm, 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. Treatment periods were separated by two-week washout intervals, and quality of life was assessed before initiating treatment and at the end of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep issues were
also evaluated. 

Findings: In the arm receiving desloratadine plus montelukast, the quality-of-life score mean (SEM) prior to treatment was 3.1 (0.41). After placebo, it decreased to 2.16 (0.43), further decreased to 1.79 (0.38) after desloratadine, to 1.48 (0.37) after montelukast, and to 1.59 (0.37) after the combination of montelukast and desloratadine. In the arm receiving montelukast plus levocetirizine, the pre-treatment quality of life score mean was 2.58 (0.49), dropping to 1.78 (0.46) after placebo, and further decreasing to 1.38 (0.42) after levocetirizine, to 1.36 (0.37) after montelukast, and to 1.26 (0.39) after the combination of montelukast
and levocetirizine. 

Conclusion: Placebo, montelukast, desloratadine, and levocetirizine all led to significant improvements in quality of life. Combining montelukast with either levocetirizine or desloratadine provided additional benefits compared to individual agents and could be considered for patients experiencing impaired quality of life due to persistent allergic rhinitis. 

In another study by Ciebiada et al, the authors evaluated the treatment outcomes of patients with persistent AR receiving montelukast, levocetirizine, desloratadine alone, or in combination with montelukast. 

Results revealed that montelukast alone, levocetirizine alone, desloratadine alone, and the montelukast/antihistamine combinations significantly alleviated nasal symptoms within the initial 24 hours. This improvement continued to escalate over the six-week treatment period, particularly among patients receiving montelukast alone or in combination with antihistamines in both arms. Notably, patients treated with the combination of montelukast and levocetirizine exhibited significantly greater improvement on day 42 compared to day one of therapy. These findings underscore the gradual and sustained improvement in nasal symptoms achieved with montelukast alone or in combination with antihistamines over a six-week treatment duration in patients with persistent AR. 

Conclusion 

Combining montelukast and levocetirizine represents a significant advancement in AR treatment, offering enhanced symptomatic relief and improved quality of life compared to monotherapy. Moreover, its cost-effectiveness makes it a practical option for patients with affordability concerns. 

Healthcare providers should consider both clinical efficacy and economic feasibility when selecting treatment options for AR. The synergistic combination of montelukast and levocetirizine presents a balanced solution, enriching the arsenal of therapies available for AR management.  

References 

• Rathod RT, Misra D. FDC of montelukast with levocetirizine: focus on bilayer technology. J Indian Med Assoc. 2009 Aug;107(8):562-4. Erratum in: J Indian Med Assoc. 2009 Oct;107(10):734. PMID: 20112841. 
• Bjermer L, Westman M, Holmström M, Wickman MC. The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option. Allergy Asthma Clin Immunol, 2019:16;15:24. Doi: 10.1186/s13223-018-0314-1. PMID: 31015846; PMCID: PMC6469109. 
• Mahatme MS, Dakhale GN, Tadke K, Hiware SK, Dudhgaonkar SD, Wankhede S. Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial. Indian J Pharmacol, 2016;48:649-53. 
• Pawankar R, Mori S, Ozu C, Kimura S. Overview on the pathomechanisms of allergic rhinitis. Asia Pac Allergy, 2011;1:157-67. Doi: 10.5415/apallergy.2011.1.3.157. Epub 2011 Oct 11. PMID: 22053313; PMCID: PMC3206239. 
• Nur Husna SM, Tan HTT, Shukri N, Mohd Ashari NS and Wong KK. Allergic Rhinitis: A Clinical and Pathophysiological Overview. Front Med, 2022. Doi: 10.3389/fmed.2022.874114 
• Panchal S, Patil S, Barkate H. Evaluation of efficacy and safety of montelukast and levocetirizine FDC tablet compared to montelukast and levocetirizine tablet in patients with seasonal allergic rhinitis: a randomized, double blind, multicentre, phase III trial. Int J Otorhinolaryngol Head Neck Surg, 2021;7:83-90. 
• Ciebiada M, Ciebiada MG, Kmiecik T, DuBuske LM, Gorski P. Quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine. J Investig Allergol Clin Immunol. 2008;18(5):343-9. PMID: 18973097. 
• Ciebiada, Maciej & Gorska-Ciebiada, Malgorzata & Barylski, Marcin & Kmiecik, Tomasz & Gorski, Pawel. Use of Montelukast Alone or in Combination with Desloratadine or Levocetirizine in Patients with Persistent Allergic Rhinitis. American journal of rhinology & allergy. 2011:25. e1-6. 10.2500/ajra.2011.25.3540.