Managing allergic rhinitis and asthma: Analyzing the role of Montelukast-Levocetirizine combination

Asthma is a heterogeneous disease encompassing a variety of respiratory symptoms like cough, shortness of breath, wheezing, or chest tightness, and the presence of a variable expiratory airflow limitation. (4) Studies showed that rhinitis is a significant risk factor for developing asthma both in adults and children. (5)

Research documents Allergic rhinitis to be affecting 10% and 30% of all adults and 40% of children globally (6), depending on the population studied. According to a survey among the Indian population, as high as 20 – 30% of Indians suffer from allergic rhinitis; whereas symptoms of rhinitis were reported in 75% of and 80% of asthmatic adults. (7)

Usually regarded to be IgE-mediated hypersensitivity to aeroallergens, allergic rhinitis has been categorized into 2 types; seasonal and perennial. Aggravating due to a complex allergen-driven mucosal inflammation owing to an interplay between resident and infiltrating inflammatory cells, allergic rhinitis if not controlled at the earliest can lead to severe long term complications like chronic sinusitis, aggravation of nasal polyps, permanent hearing impairment (as a result of chronic otitis), sleep apnea and complications thereof, craniofacial abnormalities, decreased long-term productivity and increased propensity to develop asthma. (8)

Effective Treatment of allergic rhinitis is aimed to achieve quick and optimal symptom control, not only over the entire day but also at night (9). Due to its high prevalence rates and the tendency of causing significant medical impact if poorly controlled, timely management of RH remains a challenge to physicians. This article re-evaluates the role of the 2 most widely used drug combinations – Montelukast (a leukotriene receptor antagonist) and levocetirizine (a second-generation antihistamine) in controlling allergic rhinitis successfully.

Allergic rhinitis and asthma – how are they linked?

A 10-fold higher rate of asthma has been reported in patients with allergic rhinitis than in those without it. (10) Moreover, the severity of rhinitis has been associated with the severity of coexisting asthma. (10) Such high associations between these 2 diseases have been explained based on similar anatomy of upper and lower airways and common inflammatory mediators (triggers).

With recent evidence confirming that rhinitis and asthma are closely related to each other epidemiologically, clinically, and pathophysiologically, international treatment guidelines, including Allergic Rhinitis and its Impact on Asthma (ARIA) currently recommend that clinicians check for the presence of asthma in patients with allergic rhinitis, and vice versa, so that an integrated therapeutic approach for the 2 diseases can be appropriately applied. (11)

Role of Montelukast and Levocetirizine in allergic rhinitis and asthma

Levocetirizine: MOA- Antihistamines are effective in reducing pruritis, sneezing, and watery rhinorrhea and are considered to be the first-line therapy for allergic rhinitis. Second-generation antihistamines have become increasingly popular because of their comparative efficacy and lower incidence of adverse effects relative to their first-generation counterparts. (12)

Levocetirizine, a potent second-generation antihistamine is approved for the relief of early phase symptoms of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) in adults and children aged > 6 years. (13)

Montelukast: MOA- It competitively and reversibly inhibits cysteinyl leukotrienes (CysLTs), specifically leukotrienes D4 (LTD4); which is one of the most important inflammatory mediators of RH. Exhibiting prominent anti-inflammatory and bronchodilator properties, (14) Studies have highlighted that Montelukast provides significant relief from symptoms of seasonal allergic rhinitis and associated asthma, making it comparable in potency to antihistamines. (14) Montelukast also effectively inhibits cysteinyl leukotriene receptors and reduces daytime and nighttime nasal (ie, late-phase) symptoms of patients with rhinitis. (9)

Ample evidence now affirms that the combination therapy of montelukast with antihistamine provides enhancing and complementary effects,(15) thereby reducing the symptoms more effectively. Supporting studies point out that concomitant levocetirizine and montelukast treatment are better as compared to monotherapy with levocetirizine on quick control of symptoms and quality of life in AR. (9)

How effective is the combination vs monotherapy or other combinations-quoting studies

Early studies had confirmed that concomitant therapy of levocetirizine with montelukast showed statistically significant improvement in nasal symptoms as compared to monotherapy. (15,16)

Evaluating the effect of combination therapy of montelukast and levocetirizine on the Indian population, researchers concluded that the overall daytime nasal symptoms score was way superior with the combined therapy as compared to monotherapy with either drug. The team further elaborated that secondary endpoints and global impression results are also supporting the therapeutic benefit of fixed-dose combination over monotherapy. (17)

A unique comparative study analyzing the cost-effectiveness of montelukast-levocetirizine vs montelukast-fexofenadine in patients of allergic rhinitis noted that the cost of the montelukast-levocetirizine group was Rs. 6.6 per day whereas it was Rs. 10.07 per day in the montelukast-fexofenadine group, thus concluding montelukast-levocetirizine combination was cost-effective as compared to montelukast-fexofenadine for the treatment of AR. This study has special implications in developing countries like India patients where patients have less affordability for costly medicines. (18)

Yet another study by Ciebiada M et al., found that the combination of antihistamine and montelukast produced a substantially greater improvement, especially for congestion score, in comparison with antihistamine and montelukast administered separately (19). They also reported that a combination of montelukast levocetirizine is more effective than monotherapy for persistent allergic rhinitis.

A study by Mi-Kyeong Kim et al, investigating the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma concluded that the combination was more effective than monotherapy and also demonstrated a safe and well-tolerated profile. (20)

A study by Vipan Gupta et al., reported that montelukast, a leukotriene receptor antagonist with levocetirizine is effective and safe in Indian patients of allergic rhinitis and may be of more clinical utility in the alleviation of residual symptoms and improvement of quality of life associated with allergic rhinitis. (15)

Current guidelines

The multi-disciplinary expert panel from the International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR: AR) documents that combination therapy is an effective therapy in patients whose symptoms are incompletely controlled with oral antihistamine monotherapy, with particular emphasis in a subset of patients with concurrent asthma. (10)

Key pointers

1. Allergic Rhinitis, if left untreated can quickly exacerbate severe complications. Further, estimates reveal that 80% of patients with asthma have allergic rhinitis. Under such scenarios rapid and optimal drug therapy is regarded to be the mainstay of successful management.

2. The therapeutic effectiveness of treating nasal symptoms is enhanced by a combination of levocetirizine and montelukast, thus affecting inhibition of both early- and late-phase reactions in allergic rhinitis. This drug combination has a time-tested efficacy profile and has proven its superiority in managing the early and late phase symptoms of AR and asthma.

Conclusion

Acknowledging the extensively documented efficacy of montelukast-levocetirizine in allergic rhinitis, physicians should be well aware of the pros and cons of this combination. Standing the test of time successfully, this combination therapy can go a long way in alleviating allergic rhinitis and associated co-morbidities, including asthma, in an unprecedented way.

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