Efficacy and Safety of Montelukast with Fexofenadine in Allergic Rhinitis

Allergic Rhinitis (AR) can be an intermittent or persistent, seasonal or perennial immunologic inflammatory condition affecting the nasal mucosa. Sneezing, itching of the nose, eyes, and throat, rhinorrhea, and nasal congestion with positive IgE reaction to specific allergen triggers form the features of this frequently encountered condition. AR can be associated with other comorbid conditions like asthma, eczema, chronic or recurrent sinusitis, cough, tension, and migraine headaches. It impairs the quality of life and causes a significant healthcare burden (1).

Early and Late Phase Reactions in AR:

Upon exposure to allergens, histamine, a preformed mediator is immediately released from the mast cells. This triggers early-phase reactions like sneezing, itching, and rhinorrhea. A late-phase allergic response occurs due to infiltration of histamines into nasal mucosa leading to nasal congestion. Leukotrienes also have an inflammatory effect on the upper airways leading to increased nasal blood flow and secretions (2).

Advancements in AR management:

AR and patient care management has significantly improved over the past few decades owing to the various guidelines developed by Allergic Rhinitis and its Impact on Asthma (ARIA) and others. Prompt diagnosis, allergen avoidance, and pharmacotherapy are the mainstay of treatment for AR. Antihistamines (AH), intranasal corticosteroids, leukotriene receptor antagonists (LTRAs), decongestants, mast cell stabilizers, cromolyn, immunotherapy, probiotics, and biologics are some of the management options for AR (3).

Importance of Considering LTRAs and AH in AR:

The rationale behind using LTRAs like montelukast and AH like fexofenadine for AR is due to the involvement of histamine and cysteinyl leukotrienes (LTs) in the allergic response (2). LTRAs and AH are the commonly prescribed drugs for AR as LTRAs block cysteinyl leukotriene-activated inflammation in the nasal lavage fluids and airways thus attenuating nasal obstruction and rhinorrhea whereas AHs selectively inhibit histamine 1 receptor (H1R)-mediated vaso-permeability and vasodilatation attenuating rhinorrhea and congestion (4).

Complementary effects of LTRAs with AHs:

AHs improve the daytime nasal symptoms of AR like stuffy, runny, and itchy nose and sneezing. LTRAs improve the nighttime symptoms of AR like nasal congestion on awakening, difficulty going to sleep, and nighttime awakenings (4). These two drugs are used in combination as they are more effective than monotherapy. They both block the two important mediators of inflammation with complementary effects thus effectively reducing the symptoms.

Montelukast is a type 1 cysteinyl LT receptor antagonist and its anti-inflammatory effect is aimed at treating seasonal and perennial allergic rhinitis while fexofenadine, an active metabolite of terfenadine, is a selective antagonist of the H1 receptor that does not cross the blood-brain barrier and has anti-inflammatory properties for treating AR (5).

Review of literature:

Montelukast Fexofenadine(MF) FDC more efficacious than Montelukast Levocetirizine(ML) FDC:

A randomized, open-label, prospective, two-arm, comparative, multicentric study evaluated the efficacy and safety of montelukast 10 mg + fexofenadine 120 mg (MF group) fixed-dose combination (FDC) with montelukast 10 mg + levocetirizine 5 mg FDC (ML group) in AR administered once daily for 14 days. The study reported that the total symptom score (nasal symptoms + ocular symptoms) was more effectively reduced in the MF group (93.86%) than in the ML group (87.71%).

The total nasal symptoms score and the ocular symptom score reduction were better in the MF group (92.52% and 95.34%) than in the ML group (85.58% and 92.23%) respectively suggesting that montelukast + fexofenadine was more efficacious than montelukast + levocetrizine for symptom reduction.

Montelukast Fexofenadine (MF) FDC also showed a better Global impression score for efficacy and tolerability by investigators and patients based on their response to the therapy than the Montelukast Levocetirizine (ML) suggesting that the MF combination is more efficacious than ML (6).

Take home points:

• Allergic Rhinitis (AR) is an IgE-mediated immunologic inflammatory condition of the nasal mucosa. It often co-exists with other conditions like asthma, eczema and impairs quality of life, and causes significant burden to health care.
• AR involves early and late-phase reactions mediated by histamines and leukotrienes
• Among various medications prescribed AH and LTRAs are widely utilized medications for AR/ AH reducing daytime symptoms while LTRAs improve nighttime symptoms.
• Literature shows that Montelukast + Fexofenadine is more efficacious, safe, and tolerable than Montelukast + Levocetirizine.

References:

1. Bernstein JA, Bernstein JS, Makol R, Ward S. Allergic Rhinitis: A Review. JAMA. 2024;331(10):866-877. doi:10.1001/jama.2024.0530.

2. White M, Rothrock S, Meeves S, Liao Y, Georges G. Comparative effects of fexofenadine and montelukast on allergen-induced wheal and flare. Allergy Asthma Proc. 2005;26(3):221-228.

3. Linton S, Burrows AG, Hossenbaccus L, Ellis AK. Future of allergic rhinitis management. Ann Allergy Asthma Immunol. 2021;127(2):183-190. doi:10.1016/j.anai.2021.04.029

4. 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;17(1):62. Published 2021 Jun 29. doi:10.1186/s13223-021-00564-z

5. Everardo PG, Magdalena GS, Maria Elena GP, Vanessa CM, Gabriela SC. Bioavailability assessment of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously. Allergol Immunopathol (Madr). 2021;49(4):15-25. Published 2021 Jul 1. doi:10.15586/aei.v49i4.89

6. Nayak Prateek, Drinivas CV, Chandrasekharan S. A randomized, open-label, prospective, comparative, multicentric study to evaluate the efficacy and safety of montelukast and fexofenadine fixed-dose combination vs montelukast and levocetrizine fixed-dose combination in allergic rhinitis. Indian journal of clinical practice. August 3, 2013;24(3).