Safety and Tolerability of Treatments for Allergic Rhinitis in Children

Allergic rhinitis is a common condition in adults and children and can have a large impact on patients’ health and quality of life. The aim of current allergic rhinitis therapies is to treat the subjective symptoms and to improve objective measures of the disease. Of the available treatment options for paediatric allergic rhinitis, the newer oral antihistamines and intranasal corticosteroids are first-line treatments.

First-generation antihistamines are associated with unwanted adverse effects such as cardiotoxicity, sedation and impairment of psychomotor function. Despite results from studies using first-generation antihistamines demonstrating impairment of cognitive and academic function in children, many of these agents are still commonly given to patients. The newer antihistamines, developed with the aim of being more specific for the histamine H₁ receptor and of overcoming these adverse effects, are the medication of choice in patients with mild intermittent allergic rhinitis. For children <12 years of age, three newer oral antihistamines are currently available: cetirizine, loratadine and fexofenadine. A lack of adverse effects with these antihistamines has been demonstrated in children using EEG and psychomotor performance tests, and in clinical studies. However, issues of receptor selectivity and the potential for CNS adverse effects still remain, and further studies are warranted.

Intranasal corticosteroids are the most effective anti-inflammatory agents used for the treatment of paediatric allergic rhinitis; however, the safety of these compounds remains controversial. The safety implications associated with corticosteroids are long-term, dose-related systemic effects, such as suppression of adrenocortical function, growth and bone metabolism, and the extent of these effects is influenced by a number of factors including corticosteroid type, pharmacokinetic profile, mode of delivery and delivery device. Topical corticosteroids were introduced to reduce the systemic effects seen with the long-term use of oral agents. The intranasal corticosteroids currently available for the treatment of paediatric allergic rhinitis — beclometasone, budesonide, flunisolide, fluticasone propionate, mometasone and triamcinolone — have short half-lives and rapid first-pass hepatic metabolism; however, their pharmacokinetics vary in terms of systemic absorption, potency, binding affinity, lipophilicity, volume of distribution, and half-life. A number of studies — utilising hypothalamic-pituitary-adrenal axis function tests such as plasma cortisol levels, 24-hour urinary-free cortisol tests; stimulation tests with corticotropin (adrenocorticotropic hormone), lypressin, and corticotropin-releasing hormone; and growth assessment studies using knemometry and stadiometry — have indicated that these intranasal corticosteroids are well-tolerated in paediatric patients and do not significantly affect growth.

The wealth of clinical data and the recommendations from evidence-based guidelines suggest that both antihistamines and intranasal corticosteroids have good safety profiles in children. Nevertheless, growth should be regularly monitored in children receiving intranasal corticosteroids. Other treatments such as immunotherapy, local chromones and decongestants can also be beneficial in managing paediatric allergic rhinitis, and therapies should be considered on an individual basis.