Practice Patterns About Management of Allergic Rhinitis: Indian HCP KAP Experience in 2024 and Preference of Fexofenadine and Montelukast

Allergic Rhinitis (AR) is the most common immune-mediated inflammatory condition affecting the nasal mucosa (1) triggered by the production of IgE antibodies on exposure to an allergen leading to nasal passage inflammation (1,2). It affects 40% of the global population and 22% of adolescents in India. About 9.8% of the symptoms begin in childhood and adolescence. Urbanization, environmental changes, geography, seasonal variations, lifestyle changes, and pollution are some risk factors that precipitate AR (2).

Management of Allergic Rhinitis (AR) – Overview:

Allergic Rhinitis (AR) management aims to improve the affected individuals' symptoms and quality of life. Allergen avoidance, pharmacotherapy, and immunotherapy are the management strategies for AR. Allergic Rhinitis and its Impact on Asthma and British Society for Allergy and Clinical Immunology guidelines have put forward general clinical management guidelines that include allergen avoidance and oral or intranasal antihistamines or leukotriene receptor antagonists, oral/nasal decongestants ± nasal irrigation, intranasal corticosteroids, ipratropium, and immunotherapy (3).

Indian Medical Association has put forward management guidelines, including allergen avoidance and other medications like antihistamines and leukotriene receptor antagonists (LTRAs). The guidelines also recommended using LTRAs in combination with antihistamines due to their synergistic effect in improving nasal symptoms in the first 24 hours to 6 weeks (4). Among the various medications used, antihistamines, leukotriene receptor antagonists, and intranasal corticosteroids are the commonly used drugs for AR(5).

Combining Antihistamines plus Leukotriene Receptor Antagonists (LTRA) for AR: Synergy for Optimal Clinical Symptom Resolution:

The combination of antihistamines or LTRA is beneficial for individuals who cannot get relief from monotherapy (6). The anti-inflammatory effect of fexofenadine and the bronchodilator effect of montelukast can effectively reduce nasal symptoms in AR (7). Antihistamines improve daytime nasal symptoms like stuffy, runny, itchy nose and sneezing. LTRAs are effective for nighttime symptoms like nasal congestion, sleeping difficulty, and awakenings. Hence, combining antihistamines and LTRA can improve daytime and nighttime symptoms (8). Among the various types of AR, the combination can be more advantageous in perennial AR by reducing the composite nasal and ocular symptoms (9).

Fexofenadine and Montelukast Combination in Allergic Rhinitis:

Fexofenadine is a second-generation antihistamine approved by the U.S. Food and Drug Administration (FDA) that selectively antagonizes H1 receptors with reduced affinity for cholinergic and α-adrenergic receptors and minimal crossing of the blood-brain barrier (BBB), which makes it one of the least sedating antihistamines used to treat AR (10). Montelukast is an orally active, highly selective cysteinyl LTRA of leukotriene D4 that is well tolerated, mostly plasma protein bound, and has minimal distribution across the blood-brain barrier (11).

Fexofenadine and Montelukast - Review of Clinical Literature:

Montelukast + fexofenadine is more effective than Montelukast + levocetirizine:

A prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial conducted on AR patients aged 18-65 years revealed that the Montelukast-fexofenadine (10mg &120mg respectively) combination was more effective than the montelukast-levocetirizine (10mg & 5mg) group in reducing the total nasal symptom score (TNSS).

The study found that the patients' TNSS scores significantly reduced from baseline to 4 weeks based on the intensity of nasal symptoms. Symptoms like rhinorrhoea, nasal itching, nasal obstruction, and sneezing were measured using a 4-point Likert scale from 0 to 3. Thus, the study concluded that Montelukast + fexofenadine was more effective than Montelukast + levocetirizine (7).

Take Home Messages:

• AR is a common immune-mediated inflammatory condition affecting 40% of the population globally triggered by various allergens
• Allergen avoidance, pharmacotherapy, and immunotherapy are the management strategies for AR.
• Fexofenadine is a second-generation antihistamine, while Montelukast is an LTRA. Both are well-tolerated. Compared to monotherapy, the combination can improve daytime and nighttime symptoms.
• A combination of montelukast and fexofenadine is more effective in reducing total nasal symptom score, with better outcomes in terms of symptom relief and quality of life.

References:

1. Gupte V, Thakur G, Upadhyaya A, Jain S, Bhargava S. A Perception-Based Survey on Practice Patterns About the Diagnosis and Management of Allergic Rhinitis in India. Cureus. 2024 Feb 27;

2‌. S M, M KK. Prescription trends and patterns for allergic rhinitis treatment in clinical practice. International Journal of Otolaryngology Sciences. 2024 Jan 1;6(1):01–5.

‌3. Siddiqui Z, Walker A, Pirwani M, Tahiri M, Syed I. Allergic rhinitis: diagnosis and management. British Journal of Hospital Medicine. 2022 Feb 2;83(2):1–9.

4. Indian Medical Association (IMA). Allergic Disorder: Simplify Allergic Management in India. Retrieved on 16th October 2024. IMAHQ_Allergy Booklet_2.pdf.

5. Abdullah B, Abdul Latiff AH, Manuel AM, Mohamed Jamli F, Dalip Singh HS, Ismail IH, Jahendran J, Saniasiaya J, Keen Woo KC, Khoo PC, Singh K, Mohammad N, Mohamad S, Husain S, Mösges R. Pharmacological Management of Allergic Rhinitis: A Consensus Statement from the Malaysian Society of Allergy and Immunology. J Asthma Allergy. 2022 Aug 2;15:983-1003. doi: 10.2147/JAA.S374346. PMID: 35942430; PMCID: PMC9356736.

6. Maladkar M, Patil S, S Kamble. Role of Antihistamine and Leukotriene Receptor Antagonist in Allergic Rhinitis Management: Newer Perspectives. The Indian Practitioner [Internet]. 75(6):28–34. Available from: https://www.researchgate.net/profile/Manish-Maladkar/publication/361814914_Role_of_Antihistamine_and_Leukotriene_Receptor_Antagonist_in_Allergic_Rhinitis_Management_Newer_Perspectives/links/62c6bc53959dc1752ff7c38a/Role-of-Antihistamine-and-Leukotriene-Receptor-Antagonist-in-Allergic-Rhinitis-Management-Newer-Perspectives.pdf

7. 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 Nov-Dec;48(6):649-653. doi: 10.4103/0253-7613.194854. PMID: 28066101; PMCID: PMC5155464.

8. Feng Y, Meng YP, Dong YY, Qiu CY, Cheng L. Management of allergic rhinitis with leukotriene receptor antagonists versus selective H1-antihistamines: a meta-analysis of current evidence. Allergy Asthma Clin Immunol. 2021 Jun 29;17(1):62. doi: 10.1186/s13223-021-00564-z. PMID: 34187561; PMCID: PMC8243504.

9. Liu G, Zhou X, Chen J, Liu F. Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists for Allergic Rhinitis: A Meta-analysis. Otolaryngology–Head and Neck Surgery. 2018 Jan 16;158(3):450–8.

10. Craun KL, Patel P, Schury MP. Fexofenadine. [Updated 2024 Feb 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556104/.

11. Lagos JA, Marshall GD. Montelukast in the management of allergic rhinitis. Ther Clin Risk Manag. 2007 Jun;3(2):327-32. doi: 10.2147/tcrm.2007.3.2.327. PMID: 18360641; PMCID: PMC1936314.