Allergens in India and its Avoidance: Review through Indian Guidelines and Role of Fexofenadine-Montelukast Combination

India's most common allergy sources are pollen grains, fungal spores, foods, insects, and dust mites. Allergens are classified as inhalants, ingestants, injectants, or contactants. (3)

Major Allergens In India And Their Impact On Quality Of Life

A study that analyzed the complex nature of indoor and outdoor allergens significant to the Indian population demonstrated the commonalities and variances in aeroallergens across India. According to the data, 83 pollens, 34 fungi, 6 dust mites, and 19 insect species were recorded as allergic in India, frequently contributing to high allergenic exposure in indoor and outdoor contexts. (4)

According to recent research on allergic rhinitis patients in Chennai (India), the proportion of patients allergic to home dust mites was the most prevalent, followed by pollen (84.6%), Parthenium (76.9%), cockroach (75%), cotton dust (65.4%), and Aspergillus (61.5%). (5)

One cross-sectional study conducted among Indian allergic rhinitis and/or bronchial asthma patients showed that house dust mites (41%) were the most common offending aeroallergen. House dust mite was the foremost allergen in patients with allergic airway disease from Southwestern Maharashtra, a region of India. (6)

The primary goal of treatment for allergic rhinitis is to alleviate symptoms while preventing disease progression and treatment complications. Patient education, avoidance of allergens, and adjunctive treatment are all part of managing allergic rhinitis, in addition to pharmacotherapy. (7)

Avoidance Measures Against Allergens-

The Indian Guidelines for Diagnosis of Respiratory Allergy endorsed by The Indian College of Allergy, Asthma and Applied Immunology (ICAAI), National Centre of Respiratory Allergy, Asthma and Immunology (NCRAAI) South Asia Association of Allergy, Asthma and Clinical Immunology (SAAAACI) acknowledged that a broader understanding of indoor and outdoor allergens, combined with a detailed history, could help guide in appropriate allergen testing, either by skin prick test or specific IgE testing to a specific allergen, which will aid in allergen avoidance and the design of allergen-specific immunotherapy. (3)

Indian researchers supported by the Department Of Science And Technology, Government Of India, proposed strategies at four levels for avoiding allergens and preventing the incidence of allergic diseases/illnesses in India. They recommend following proactive measures to minimize exposure to pollen at the individual level. This includes staying indoors during peak pollen times, using air purifiers in homes and offices, and keeping windows closed. They also suggest local governments implement urban planning strategies that prioritize green spaces with low pollen-producing plants, monitor pollen levels and provide timely alerts to the public. They also offer enacting policies and regulations to address pollen allergy risks on a larger scale by funding more research on pollen-related diseases and implementing pollen monitoring and control guidelines at the national level. (8)

By adopting strategies at these four levels, it is possible to create a comprehensive and coordinated approach to mitigate the impact of pollen allergies and improve the quality of life susceptible to pollen-induced illnesses. (8)

The Indian Guidelines on Allergic Rhinitis formulated by the Association of Otolaryngologists of India also prioritized allergen avoidance in managing allergic rhinitis. The guideline also suggests maintaining a low-allergen environment over a prolonged period in this patient population. They indicate a skin prick test as a routine procedure to identify the specific allergen the patient is sensitized to. (7)

Pharmacological Approach: Antihistamines are an effective pharmacological treatment option for allergic rhinitis, following the understanding that histamine and its receptors play an essential role in developing allergic symptoms. (9) Antihistamines and LTRAs (Leukotriene receptor antagonists) commonly manage allergic rhinitis. The blockage or inhibition of these two mediators provides additional benefits compared to a single mediator inhibition. (10)

Fexofenadine is one of the least sedating and most receptor-specific second-generation antihistamines compared with other antihistamines. LTRAs have taken a role in the management of allergic rhinitis. (9) Among cysteinyl leukotriene receptor-1 antagonists, montelukast is the only drug approved for treating allergic rhinitis. (10)

A multicentered, prospective, randomized, placebo-controlled, parallel-group explored and compared the effectiveness of LTRA with antihistamine over antihistamine alone in controlling allergic allergic allergic rhinitis symptoms in 21 days. The study enrolled 275 patients and divided them into three groups (fexofenadine alone, fexofenadine+montelukast, fexofenadine+placebo). The fexofenadine+montelukast group improves nasal congestion (P=0.003), itching (P=0.009), sneezing (P=0.004), and rhinorrhea (P=0.001), respectively better than other groups for 21 days. The efficacy of the medication used revealed that the fexofenadine+montelukast is better than the other two groups (P=0.037). This suggest that fexofenadine+montelukast) combination therapy is more effective than fexofenadine alone in controlling allergic rhinitis symptoms. (11)

An open, randomized, 2×2 crossover study performed on 78 subjects evaluated and compared the bioequivalence of fexofenadine (120mg) and montelukast (10mg) in a fixed-dose combination tablet versus the components administered simultaneously. The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612–102.144 for the area under the curve of the plasma concentration after administration to the last concentration (AUC0-t), 88.471–102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC0–∞), and 91.413–108.544 for the maximum plasma concentration (Cmax). For montelukast, they were 96.418–108.416 for AUC0-t, 93.273–106.642 for AUC0-∞ and 94.749–110.178 for Cmax. The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%–125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses, making the combination as a new alternative for the treatment of AR. (12)

A review article about combined antihistamines and leukotriene antagonists in mono or combination therapy noted that LTRA and antihistamine effectively controlled nasal and eye symptoms and quality of life better than antihistamine alone. The combined fexofenadine montelukast significantly attenuated the response to nasal AMP (adenosine 5'-monophosphate) challenge and improved nasal symptoms compared with fexofenadine or montelukast alone. (10)

Allergic Disorders: Simplify Allergic Management in India by the Indian Medical Association noted that the combination of LTRA and antihistamine synergise in treating seasonal allergic rhinitis. In the case of perennial allergic rhinitis, the combination significantly improves nasal symptoms in the first 24 hours. Still, improvement at the end of 6 weeks was considerably more significant than that achieved on the first day of therapy in patients treated with montelukast alone or in combination therapy with the antihistamine. They also noted that Montelukast is an effective drug in allergic rhinitis to decrease nasal inflammation and limit nasal congestion, sneezing and rhinorrhea. (13)

Clinical Care Points

• Allergic diseases have become a significant public health issue worldwide, affecting more than 25% of India's population.
• Pollen, moulds, fungi, insects, pets, and various foods are the primary allergen sources in India. Along with pharmacotherapy, avoiding allergens is essential in managing allergic rhinitis.
• Multiple guidelines emphasize and prioritise the importance of avoiding allergens in managing the spectrum of allergic diseases.
• Pharmacotherapy, including antihistamines and leukotriene receptor antagonists, is vital in managing allergy symptoms effectively.
• Antihistamines and LTRAs are frequently used in the treatment of allergic rhinitis. The blockage or inhibition of these two mediators may provide additional benefits compared to a single mediator inhibition.
• Fexofenadine, a second-generation antihistamine combined with montelukast, has shown significant efficacy in managing allergic rhinitis.