Evidence for Clinical Safety, Efficacy, and Parent and Physician Perceptions of Levocetirizine for the Treatment of Children with Allergic Disease

Abstract

Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are highly burdensome diseases, which are increasing in prevalence, especially in the paediatric population. Despite the availability of a large number of medications for treatment of AR and CIU, their use in children has primarily been based on data obtained from a limited number of clinical trials in children and/or testing in adults. The H₁-antihistamines have traditionally been used as first-line treatment for the relief of both AR and CIU symptoms in children. The first-generation H₁-antihistamines are associated with marked adverse effects such as sedation, sleepiness/drowsiness as well as difficulties in learning and cognitive processing; thus, they are recommended for limited or discontinued use in children with AR or CIU. In contrast, second-generation H₁-antihistamines are more adapted for the use in children with AR and CIU due to better safety profiles. However, only a limited number of trials with these agents have been conducted and generally, data from well-designed trials in children are lacking. Levocetirizine is one of the most extensively investigated H₁-antihistamines for its pharmacologic properties, safety, efficacy as well as overall global satisfaction in children aged 2–12 years. Levocetirizine is the only H₁-antihistamine launched in the 21st century shown to lack clinically relevant adverse effects on physical and psychomotor development or routine laboratory tests over a long-term period of 18 months in 1- to 3-year-old children predisposed to development of allergic disease. Available data suggest that levocetirizine is a suitable treatment option for AR and CIU in children aged 6 months to 12 years.

Off-label prescribing for allergic diseases in children

“…However, the absorption, distribution and metabolism in children diverge from adults and age-related differences in children exist in their ability to metabolize, absorb, excrete and transform medications, therefore efficacy and safety might be affected [59,62]. Although nasal corticosteroids can be associated with some side effects, including bone mineral density loss, adrenal suppression and growth retardation, these were only reported in one study using beclomethasone [60,62]. Therefore, only the lowest possible dose for symptoms control is favored [61].…”

“…In other studies assessing systemic anti-histamines, off-label prescribing ranged from 6.5% to 43% [17,23,30,33,35]. Cetirizine [65,66], levocetirizine [62,67] and loratadine [68] have been the most investigated for long term safety in pediatric population. Despite pharmacokinetic studies have been performed in new generation anti-histamines, long-term safety studies in children are still lacking [69,70].…”

“…Despite pharmacokinetic studies have been performed in new generation anti-histamines, long-term safety studies in children are still lacking [69,70]. Indeed, due to the proven efficacy of nasal corticosteroids and anti-histamines on disease control in children by reducing disease-associated impairment and improving disease-related quality of life, more studies are needed about safety in order for physicians to perform a rational decision of the large number of options available in the market [62,69,71]. …”

“…Children pediatric formulations, namely under 6 years of age, are usually liquid and it is necessary to make them stable, sterile, pleasant and long lasting. Furthermore as children grow, drug doses should be adapted to weight and, to avoid dosing errors, the means to deliver accurate doses of these liquid formulations need to be available [62]. In atopic dermatitis, anti-histamines also are considered as potential benefit to reduce pruritus, and although no evidence exists to support their role in treatment they can be useful in reducing this disturbing symptom in children [69].…”

Update on Antihistamine Treatment for Chronic Urticaria in Children

“…Evidence demonstrates that levocetirizine is safe and well tolerated in children. Its use is approved in Europe for children ≥2 years of age [19,24,25].…”