Indian Guidelines Review on Allergic Rhinitis and Scope for Use of Fexofenadine and Montelukast Combination

AR is often accompanied by other comorbidities such as asthma, nasal polyps, sinusitis, and allergic dermatitis. (2) The CARAS (Coexistence of Allergic Rhinitis and ASthma) survey pointed out that 65.24% of individuals suffered from co-existing AR and asthma. (3)

Risk Factors: House dust mites and fungal sensitisation are significant indoor allergens. Passive smoking, cooking with firewood, exposure to second-hand smoke, contact with pets or domestic animals, and use of drugs like paracetamol and antibiotics are other common risk factors. Poor waste management practices like open dumpsters also contribute to aeroallergen exposure. (1)

Review of Indian Guidelines

Indian Medical Association: Recommendations for Management of Allergic Rhinitis: ‘Allergic Disorder: Simplify Allergic Management in India,' a document formulated by The Indian Medical Association for Simplifying the Management of Allergic Rhinitis, has put forward recommendations for the effective stepwise management of allergy in the Indian scenario. Some of the relevant points have been elaborated:(4)

• Avoidance of allergens.
• In intermittent symptoms (<4 days per week) and mild to moderate-severe cases, the treatment should be the administration of second-generation antihistamines, intranasal H2 blockers or nasal decongestants and Leukotriene Receptor Antagonists (LTRA).
• In persistent symptoms (> 4 days a week or > four weeks per year) along with the pharmacological treatment, if the symptoms persist after 2-4 weeks, step up the dose or continue for one month.
• Second-generation antihistamines such as fexofenadine, levocetirizine, cetirizine, and bilastine have been recommended to treat AR.
• Leukotriene receptor antagonists like montelukast and zafirlukast have also been suggested for treating AR.
• The recommendations also advised using LTRA in combination with antihistamines, given the synergistic effect in treating seasonal AR. The combination has shown better efficacy in improving nasal symptoms for perennial AR than montelukast alone.

Allergic Rhinitis- Standard Treatment Guidelines by the Indian Academy of Pediatrics indicated allergen avoidance in diagnosed AR patients. For pharmacological treatment, they suggested using a combination treatment of LTRA and second-generation antihistamines. The guideline also noted that second-generation antihistamines, including fexofenadine, are preferred in mild intermittent AR for a better safety efficacy ratio. (6)

Combining antihistamines and LTRAs may offer multimodal action through broader inhibition of these mediators, leading to enhanced therapeutic effects and improved symptom relief in patients. Montelukast is classified as a Leukotriene Receptor Antagonist (LTRA) that blocks the cysteinyl leukotriene receptor, specifically LTC4, LTD4, and LTE4. Antihistamines such as fexofenadine are commonly used to treat these symptoms as they have a similar mechanism of blocking H1 receptors and reducing symptoms of allergic rhinitis. (5)

Fexofenadine is a second-generation antihistamine that is derived from terfenadine. Unlike older antihistamines, fexofenadine has minimal anticholinergic effects and does not significantly bind to cholinergic and alpha-adrenergic receptors. Additionally, it can inhibit the release of inflammatory mediators from mast cells and other inflammatory cells. When taken orally, fexofenadine is quickly absorbed and reaches peak concentrations in the bloodstream within an hour. (7) Montelukast is the only anti-leukotriene approved for allergic rhinitis and is this class's most often utilised agent. (8)

• A study conducted by Anurag Pathak et al. compared the efficacy of montelukast levocetirizine combination with montelukast fexofenadine combination in AR management. The study enrolled 40 Indian patients with AR; 20 patients were treated with a montelukast levocetirizine combination, and another 20 patients were treated with a montelukast fexofenadine combination for four weeks. The evaluation of TNSS (total nasal symptom score), that is, the intensity of nasal symptoms (rhinorrhea, nasal itching, nasal obstruction, and sneezing), showed a significant reduction in the montelukast fexofenadine group (p=0.45) in two weeks and further improvement was observed at four weeks in the same group (p=0.00). The study concluded that montelukast fexofenadine is a comparatively better treatment option in treating AR patients. (9)
• A prospective comparative parallel-group study compared the efficacy of montelukast-fexofenadine and montelukast-levocetirizine combination treatment in mild persistent or moderate to severe intermittent Indian AR patients. The study enrolled 60 subjects, who were divided into two groups. One group received montelukast (10mg)-levocetirizine (5mg) once daily dose; the other group received montelukast (10mg)-fexofenadine (120mg) once daily at bedtime for 30 days. The total nasal symptom scores (TNSS), including rhinorrhea, nasal obstruction, sneezing and nasal itching, showed a significant reduction (p<0.001) in the Montelukast-fexofenadine group in 15 days. This suggests that montelukast-fexofenadine is efficacious and safe in Indian AR patients. (10)

• Allergic rhinitis is a significant public health concern in India, affecting patients' quality of life.
• Multiple Indian guidelines have put forth treatment algorithms for allergic rhinitis. The management of AR includes using second-generation antihistamines, intranasal corticosteroids, leukotriene receptor antagonists, and their combination with antihistamines.
• Combining antihistamines and LTRAs may offer multimodal action through broader inhibition of these mediators, leading to enhanced therapeutic effects and improved symptom relief in patients.
• Fexofenadine is a second-generation antihistamine with minimal sedation, and montelukast is the only anti-leukotriene approved for use in pediatric children.

The combination of Montelukast plus Fexofenadine exhibits notable efficacy in alleviating AR symptoms, providing a valuable treatment consideration in the appropriate AR patient population. (9,10)

References:

1. Moitra S, Mahesh PA, Moitra S. Allergic rhinitis in India. Clin Exp Allergy. 2023 Jul;53(7):765-776. doi: 10.1111/cea.14295. Epub 2023 Mar 1.

2. Barne, M., Singh, S., Mangal, D. K., Singh, M., Awasthi, S., Mahesh, P. A., Kabra, S. K., Mohammed, S., Sukumaran, T. U., Ghoshal, A. G., Sinha, S., Kochar, S. K., Singh, N., Singh, U., Patel, K. K., Sharma, A. K., Girase, B., Madas, S., Chauhan, A., … Salvi, S. Global Asthma Network Phase I, India: Results for allergic rhinitis and eczema in 127,309 children and adults. 2022 The Journal of Allergy and Clinical Immunology. Global, 1(2), 51–60.

3. Jaggi V, Dalal A, Ramesh BR, Tikkiwal S, Chaudhry A, Kothari N, Lopez M, Gogtay J. Coexistence of allergic rhinitis and asthma in Indian patients: The CARAS survey. Lung India. 2019 Sep-Oct;36(5):411-416. doi: 10.4103/lungindia.lungindia_491_18.

4. Indian Medical Association (IMA). (n.d.). Allergic Disorder: Simplify Allergic Management in India. Retrieved on 22nd October 2023 from https://www.ima-india.org/ima/pdfdata/IMAHQ_Allergy%20Booklet_2.pdf

5. Indian Guidelines on Allergic Rhinitis. Formulated by the Association of Otolaryngologists of India. 2021. Retrieved on 20th October 2023 from http://www.aoiho.org/pdf/AOI%20AR%20Guidelines.pdf

6. Indian Academy of Pediatrics. Allergic Rhinitis- Standard Treatment Guidelines. 2022. Retrieved on 23rd October 2023 from https://iapindia.org/pdf/Ch-014-Allergic-Rhinitis.pdf

7. Craun KL, Schury MP. Fexofenadine. [Updated 2022 Dec 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556104/

8. Cobanoğlu B, Toskala E, Ural A, Cingi C. Role of leukotriene antagonists and antihistamines in the treatment of allergic rhinitis. Curr Allergy Asthma Rep. 2013 Apr;13(2):203-8. doi: 10.1007/s11882-013-0341-4.

9. Anurag Pathak, Hemant Garg, Rajesh Kumar Suman, Arun Kumar Adhikari. To Compare the Efficacy of Montelukast Levocetirizine and Montelukast Fexofenadine in Patients of Allergic Rhinitis at a Tertiary Care Centre. Int J Med Res Prof. 2019 May; 5(3): 337-39. DOI:10.21276/ijmrp.2019.5.3.079

10. Soumya Annu Achankunju, S.Rajaram, K.Mukesh, Anakha Kaladharan. A Comparative Study of Efficacy and Safety of Montelukast Levocetirizine and Montelukast Fexofenadine in Patients with Allergic Rhinitis. 2022. World Journal of Pharmaceutical Research.