The late-phase reaction, which occurs hours after allergen exposure, involves the recruitment of various inflammatory cells and the release of multiple mediators, perpetuating the inflammatory response. This phase leads to nasal congestion, a distressing symptom for AR patients. Nasal and ocular symptoms significantly impact patients’ quality of life and daily functioning.

 Existing pharmaceutical options

Current pharmacological management of AR involves symptomatic relief using antihistamines, corticosteroids (oral or nasal), nasal decongestants, and leukotriene receptor antagonists. First-generation antihistamines are no longer recommended due to their central nervous system side effects and cardiac toxicity.

Newer-generation antihistamines, such as cetirizine, loratadine, and desloratadine, offer enhanced efficacy and safety profiles. Intranasal antihistamines like olopatadine, levocabastine, and azelastine ensure targeted drug delivery to the nasal mucosa.

Corticosteroids act as the first-line pharmacotherapy by suppressing immune cell infiltration in AR and are effective for both mild and moderate-severe cases. Combination therapies, such as intranasal H1 antihistamines with intranasal corticosteroids, have demonstrated superior outcomes compared to oral H1 antihistamines plus intranasal corticosteroids. Leukotriene receptor antagonists like montelukast have shown efficacy in reducing night-time symptoms, especially when used in combination with H1 antihistamines.

Nasal decongestants provide relief from nasal congestion symptoms by reducing mucosal swelling, but overuse can lead to rebound congestion (rhinitis medicamentosa), which can be treated with intranasal corticosteroids.

New research on combination therapy

Panchal et al (2021) conducted a Phase III, multicentre, randomised, double-blind study to evaluate the efficacy, safety, and tolerability of a fixed-dose combination (FDC) of montelukast 10mg and levocetirizine 5mg compared to either montelukast 10mg or levocetirizine 5mg alone in patients with seasonal allergic rhinitis (SAR). The study included various efficacy measures, including daytime nasal symptoms score, night-time symptoms score, daytime eye symptom score, patient’s global evaluation, physician’s global evaluation, and rhino-conjunctivitis quality-of-life score.

Results showed that the FDC group had a statistically significant improvement in daytime nasal symptoms score compared to the monotherapy groups. The FDC also demonstrated superiority in secondary efficacy endpoints, such as night-time symptoms score, daytime eye symptoms score, and rhino-conjunctivitis quality-of-life scores. The FDC of montelukast and levocetirizine was found to be safe and well-tolerated, with most adverse events being mild and unrelated to the study medication.

In another study by Mahatme et al (2016), the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combinations were compared in patients with AR. Results indicated a significant reduction in the total nasal symptom score in both groups, with the montelukast-fexofenadine group showing a more pronounced reduction. However, the cost-effectiveness ratio favoured the montelukast-levocetirizine combination.

Conclusion

The combination of montelukast and levocetirizine has emerged as an effective treatment option for AR, offering enhanced symptomatic relief compared to monotherapy. This combination not only improves symptoms but also enhances the quality of life of AR patients.

Furthermore, combining montelukast with levocetirizine demonstrates cost-effectiveness, making it a practical choice for patients who may have affordability concerns with more expensive alternatives.

In the management of AR, healthcare providers should consider not only the clinical efficacy but also the economic feasibility of treatment options. The combination of montelukast and levocetirizine appears to strike a balance between efficacy and affordability, making it a valuable addition to the arsenal of treatments for AR.

References

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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.