Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adults

Abstract

What is already known about this subject • According to recent literature, the pathophysiologies of allergic rhinitis and chronic idiopathic urticaria are thought to be similar in adults and children. In addition, the response to antihistamine treatment is similar in adults and children, suggesting a similar concentration-response relationship.• However, an appropriate dose selection and the pharmacokinetics of desloratadine in children of Ն6 months-Յ2 years old have never been addressed in the literature. What this study adds• This study demonstrated that desloratadine syrup offers a safe treatment option for allergic conditions in young children.• A suitable dose for children aged Ն6 months-<1 year is 1.0 mg, while the corresponding predicted dose for children aged Ն1 year-Յ2 years is 1.25 mg. These paediatric doses yielded similar systemic desloratadine exposures (AUC) to those seen with a typical adult dose of 5.0 mg. AimsThe aim of this study was to identify the dose of desloratadine in children aged Ն6 months-Յ2 years that would yield a single-dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup. MethodsIn a phase 1, single-dose, open-label, pharmacokinetic study in 58 children aged Ն6 months-<1 year and Ն1 year-Յ2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events. ResultsThe apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged Ն6 months-<1 year was 27.8 l h -1 (35) and corresponding values in children Ն1 year-Յ2 years was 35.5 l h -1 (51), compared with 137 l h -1 (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for Ն6 months-<1 year and 1.25 mg for Ն1 year-Յ2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues. ConclusionsDoses of 1.0 and 1.25 mg in children aged Ն6 months-Յ2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria

“…Only medications with proven efficacy and safety in the paediatric population should be used. Cetirizine, desloratadine, fexofenadine, levocetirizine, rupatadine, bilastine and loratadine have been well studied in children, and their long‐term safety has been well established in the paediatric population. In addition, the choice of the modern 2 nd ‐generation H 1 ‐antihistamines in children depends on the age and availability as not all are available as syrup or fast dissolving tablet suitable for children.…”

Efficacy and tolerability of the updosing of second‐generation non‐sedating H1 antihistamines in children with chronic spontaneous urticaria

“…The sgAH 1 s (e.g., cetirizine, desloratadine, levocetirizine, rupatadine, and loratadine) have been shown to provide long-term safety in the pediatric population for use in treating allergy diseases, such as allergic rhinitis 1,[5][6][7][8][9][10][11][12][13] . Recently, three randomized controlled trials (RCT) established the safety of second-generation non-sedating H1 antihistamines in CU 11,14,15 as well.…”

Wytyczne EAACI/GA2LEN/EDF/WAO dotyczące definicji, klasyfikacji, diagnostyki i leczenia pokrzywki

“…W populacji pediatrycznej należy stosować tylko leki o udowodnionej skuteczności i bezpieczeństwie. Cetyryzyna [155], desloratadyna [156,157], feksofenadyna [158], lewocetyryzyna [159], rupatadyna [160], bilastyna [161] i loratadyna [155] zostały dobrze przebadane u dzieci, a ich długotrwałe bezpieczeństwo zostało potwierdzone w populacji pediatrycznej. Ponadto wybór nowoczesnych leków przeciwhistaminowych drugiej generacji blokujących receptory H 1 u dzieci zależy od wieku dziecka i dostępności, ponieważ nie wszystkie leki dostępne są w postaciach odpowiednich dla dzieci, takich jak syrop czy szybko rozpuszczająca się tabletka.…”