Allergic Rhinitis in Children: Review of Indian Guidelines and Applicability of Fexofenadine

Allergic rhinitis is a common disease that frequently occurs in children and adolescents. The disease has a significant burden that impacts sleep, academic performance, and quality of life. It may also be linked to other allergy conditions, such as asthma. (1) Allergic rhinitis affects nearly 40% of children at some time in their lives. Approximately 50% of people with allergic rhinitis also have associated asthma, and almost 80% of asthmatics are affected by allergic rhinitis. (2)

AR in the Pediatric population:

Allergic rhinitis significantly impacts the pediatric population, with an increasing trend for diagnosed allergic rhinitis over the years. The overall prevalence of self-reported lifetime allergic rhinitis in children is 19.93% globally. (3) The Global Asthma Network (Phase I) study in India has reported that the prevalence of allergic rhinitis among Indian children aged 6-7 years is 7.7%. Coexisting asthma and eczema are the strongest risk factors among the same population, with the former increasing the risk by 5.7-fold and the latter by 2.6-fold, respectively. Other risk factors include parental history of atopy, maternal and paternal smoking, use of paracetamol and antibiotics during infancy, and using wood as fuel for cooking. (4)

The diagnosis of pediatric allergic rhinitis in India is commonly based on a detailed history, characteristic signs and symptoms and the confirmed presence of allergen-specific IgE (either skin prick testing or in vitro specific IgE testing) has a supportive role in the diagnosis. Tests guided by a careful history and local aerobiology are essential. (2)

Treatment with sedating antihistamines has been demonstrated to lead to diminished quality of life, impaired learning, and decreased learning performance. (5) The negative central nervous system (CNS) side effects frequently observed after using conventional antihistamines have been greatly decreased by administering second-generation antihistamines within their therapeutic dose window. (6)

Management Overview: Indian Academy of Pediatric (IAP) Guidelines for Allergic Rhinitis

The Standard Treatment Guidelines for Allergic Rhinitis 2022 by the Indian Academy of Pediatrics (IAP) emphasised the importance of integrating patient education, self-monitoring, regular physician visits, avoidance of triggers, and pharmacotherapy as the cornerstone of allergic rhinitis management. The guideline highlighted that for pharmacological treatment, second-generation antihistamines (including fexofenadine) are the drugs of choice in mild intermittent and mild persistent allergic rhinitis to achieve a better safety efficacy index. Symptoms like watery rhinorrhea, sneezing, itching of the nose, nasal congestion, and two or more symptoms for more than one hour on most days are commonly associated with Indian pediatric allergic rhinitis in children. The guideline suggested using these symptoms as a diagnosis criteria for pediatric allergic rhinitis. (2)

Fexofenadine: Practical Pharmacological Overview

Fexofenadine, an H1-receptor antagonist that is also the active metabolite of terfenadine, is reported to be free of adverse cardiovascular and central nervous system effects. The pharmacokinetics of fexofenadine found in children are similar to those reported in adults; the mean terminal elimination half-life is 14 hours (plasma concentrations monitored for only 12 hours). Fexofenadine, administered at 30 or 60 mg, suppressed the histamine-induced wheal-and-flare within 1 to 2 hours in children (mean age of 9.8 + 1.8 years) with allergic rhinitis. (7)

Figure 1: Suppression of wheals (1-8hrs) and flares (2-24hrs) with Fexofenadine (30 mg) in pediatric allergic rhinitis. Adapted from Simons, F.E et al. “The clinical pharmacology of fexofenadine in children.” The Journal of allergy and Clinical Immunology vol. 98,6 Pt 1 (1996): 1062-4. SEM-scanning electron microscope.

Fexofenadine does not cross the blood-brain barrier (BBB), inducing no sedative side effects even at higher than recommended doses. (8)

Fexofenadine in Pediatric Allergic Rhinitis: Review of Clinical Evidence

Fexofenadine Relieves Allergic Rhinitis Symptoms in Children: A pooled analysis of three double-blind, randomized, placebo-controlled trials evaluating the efficacy and safety of fexofenadine in children (aged 6–11 years) with seasonal allergic rhinitis was conducted. A total of 1810 children who received either fexofenadine HCl 30mg, 15mg, or 60mg twice daily each were included. The results showed that fexofenadine HCl 30mg twice daily was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms such as sneezing, rhinorrhea, itchy nose, ear, throat, mouth, itchy, watery, and red eyes, and nasal congestion (P<0.05). This analysis demonstrated fexofenadine, at doses of up to 60mg twice daily, is safe and non-sedating, and fexofenadine HCl 30mg twice daily effectively reduces all seasonal allergic rhinitis symptoms in children. (9)

Fexofenadine Treatment is Safe in Children: A randomized, placebo-controlled, parallel-group, double-blind study assessed the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. The study was conducted at 148 centers across 15 countries and included 935 children (aged 6-11 years) randomly treated with either fexofenadine HCl 30 mg or placebo twice daily for 14 days. Fexofenadine was significantly superior to placebo in the primary efficacy analysis, which was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes) throughout the double-blind treatment (P<=0.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P<0.05), including nasal congestion in the evening reflective assessment (P<0.05). The mean change in evening reflective individual symptom score is displayed in Figure 2. This study confirms the efficacy and safety of fexofenadine in children with seasonal allergies. (10)

Figure 2: Twelve-hour PM -reflective individual symptom scores with modified intention-to-treat (mITT) population. All P values are for the treatment group versus placebo. *P < .01. **P < .001. ***P ≤ .0001. Adapted from Wahn, Ulrich et al. “Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.” The Journal of Allergy and Clinical Immunology vol. 111,4 (2003): 763-9. doi:10.1067/mai.2003.1384.

Fexofenadine: Practical Advantages in Allergic Rhinitis in Children

• The IAP guideline recommended fexofenadine at 30–180 mg doses in children above 6 months. (2)
• Treatment with fexofenadine improves daily activity impairment and reduces classroom time missed and classroom room impairment in children with allergic rhinitis. (11)
• The relative lack of sedative effects associated with fexofenadine translates into better learning performance and decreased negative impact on other activities among children. (8)
• Fexofenadine is significantly less impairing than cetirizine, with lower subjective sleepiness than cetirizine, due to lower histamine receptor 1 occupancy than cetirizine [fexofenadine –0.1% vs 26.0%]. (8)
• No clinically significant ECG (electrocardiogram) changes have been observed from clinical studies administered fexofenadine in pediatric allergic rhinitis. The clinical studies' lack of severe adverse events and cardiac dysrhythmias indicates fexofenadine's cardiac safety. (12)
• In general, fexofenadine does not impair cognitive or psychomotor functions. It is free from adverse effects such as cardiotoxicity, including life-threatening arrhythmias, which may be potentially associated with other nonsedating antihistamines. (13)

Conclusion and Take-Home Points

• Allergic rhinitis significantly impacts the pediatric population, with an increasing trend for diagnosed allergic rhinitis over the years in India.
• Coexisting asthma and eczema are the strong associative risk factors for allergic rhinitis among 6- to 7-year-old Indian children.
• Treatment with sedating antihistamines diminished quality of life, impaired learning, and decreased learning performance among children.
• Fexofenadine is significantly less impairing than cetirizine, with lower subjective sleepiness and a relative lack of sedative effects.
• Fexofenadine effectively reduces symptoms (sneezing, rhinorrhea, itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes, nasal congestion) of allergic rhinitis and is safe in children. The consideration of fexofenadine in pediatric allergic rhinitis is backed by clinical practice guidelines.

References:

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2. The Indian Academy of Pediatrics (IAP). Standard Treatment Guidelines for Allergic Rhinitis 2022. Retrieved on 22nd February 2024 from https://iapindia.org/pdf/Ch-014-Allergic-Rhinitis.pdf

3. Licari A, Magri P, De Silvestri A, Giannetti A, Indolfi C, Mori F, Marseglia GL, Peroni D. Epidemiology of Allergic Rhinitis in Children: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2547-2556. doi: 10.1016/j.jaip.2023.05.016. Epub 2023 May 24. PMID: 37236349

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