CUSTOM DERMATOLOGY SEARCH:
Desloratadine for the Treatment of Chronic Urticaria
E. W. Monroe, MD
Desloratadine is a new selective H1-receptor antagonist and is the primary active metabolite of loratadine (Claritin®, Schering-Plough). It has been approved for use in many countries throughout the world and is sold as Clarinex® in the US, and as Aerius® in Canada. In Europe it is being marketed as Neoclarityn™ and Aerius™. During the first quarter of 2002, it received US FDA approval for the relief of both nasal and non-nasal symptoms of allergic rhinitis (seasonal and perennial) in patients ≥12 years of age. Additionally, it is indicated for the symptomatic relief of pruritus and the reduction in the number and size of hives in patients ≥12 years of age with chronic idiopathic urticaria.
Urticaria is a cutaneous reaction pattern characterized by pruritic, transient, erythematous papules and wheals often with central clearing. It results from the transudation of fluid from the cutaneous vasculature. Numerous factors both immunologic and non-immunologic, including autoantibodies, can cause mast cell activation and the release of mediators capable of causing vascular permeability, and thus, hives. Histamine is the best documented of these mediators. Numerous etiologies exist for urticaria including: drugs, foods, infections, contactants, internal diseases, psychogenic factors, genetic factors and physical factors (pressure, cold, heat, etc.). Urticaria is classified as acute or chronic depending on whether its duration is > 6 weeks. The cause of acute urticaria is usually detectable. In chronic urticaria, most cases (90-95%) are idiopathic.
Mechanism of Action and Pharmacology
Desloratadine, is a selective H1-receptor antagonist. It is approximately 10-20 times more potent in H1-receptor binding than loratadine in vitro, and has 2.5-4 times more antihistaminic potency in animals,1,2 and has no significant cholinergic or H2-receptor affinity. Furthermore, desloratadine does not penetrate the blood-brain barrier in animal studies, a fact that has been confirmed by the lack of sedation or cognitive impairment in clinical trials.
Pharmacokinetics and Drug Interactions
Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject’s age or sex. Metabolism of desloratadine does not involve the cytochrome P450 system or the pglycoprotein transport system. Results of electrocardiographic studies have revealed no clinically relevant interactions between desloratadine and erythromycin, ketoconazole or grapefruit juice.8
The efficacy and safety of desloratadine 5mg, once daily was studied in two randomized, double-blind, placebo-controlled, clinical trials of six weeks’ duration involving 416 patients, 12-84 years of age with chronic idiopathic urticaria.9,10 The primary efficacy variable, i.e., the mean improvement from baseline in pruritus over the first week of treatment, was significantly greater in the desloratadine group (47.9%) than in the placebo group (21.9%; p<.001). All secondary efficacy parameters, i.e., total symptom scores (pruritus, number and size of hives), quality of life measures (interference with sleep and daily activities), showed that desloratadine was significantly better than placebo at all time points from day 2 of treatment until the end of the study at 6 weeks.
Clinical trials have demonstrated that desloratadine has a superior efficacy and similar safety profile to placebo in the treatment of patients with chronic idiopathic urticaria. Once-daily dosing provided rapid, prolonged benefits in objective and subjective disease and quality of life measures. Desloratadine’s effectiveness was maintained for the full 24 hours after each dosing, as well as throughout the 6 week study. Further active comparator studies will determine whether desloratadine’s potent H1- antihistaminic properties combined with potential anti-allergic and anti-inflammatory effects make it superior to other current treatment options. At this time, desloratadine should be considered one of the preferred first-line treatments for patients with chronic idiopathic urticaria.
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Last modified: Thursday, 20-Feb-2014 18:01:41 MST