Update on rupatadine in the management of allergic disorders

Abstract

In a review of rupatadine published in 2008, the primary focus was on its role as an antihistamine, with a thorough evaluation of its pharmacology and interaction with histamine H1 -receptors. At the time, however, evidence was already emerging of a broader mechanism of action for rupatadine involving other mediators implicated in the inflammatory cascade. Over the past few years, the role of platelet-activating factor (PAF) as a potent mediator involved in the hypersensitivity-type allergic reaction has gained greater recognition. Rupatadine has dual affinity for histamine H1 -receptors and PAF receptors. In view of the Allergic Rhinitis and its Impact on Asthma group's call for oral antihistamines to exhibit additive anti-allergic/anti-inflammatory properties, further exploration of rupatadine's anti-PAF effects was a logical step forward. New studies have demonstrated that rupatadine inhibits PAF effects in nasal airways and produces a greater reduction in nasal symptoms than levocetirizine. A meta-analysis involving more than 2500 patients has consolidated the clinical evidence for rupatadine in allergic rhinoconjunctivitis in adults and children (level of evidence Ia, recommendation A). Other recent advances include observational studies of rupatadine in everyday clinical practice situations and approval of a new formulation (1 mg/ml oral solution) for use in children. In this reappraisal, we revisit some key properties and pivotal clinical studies of rupatadine and examine new clinical data in more detail including studies that measured health-related quality of life and studies that investigated the efficacy and safety of rupatadine in other indications such as acquired cold urticaria, mosquito bite allergy and mastocytosis.

Lipid Mediators of Allergic Disease: Pathways, Treatments, and Emerging Therapeutic Targets

“…PAF-mediated eosinophil chemotaxis occurs by two distinct signaling pathways (monomeric and dimeric PAFR signaling). Monomeric PAFR signaling drives eosinophil chemotaxis whereas the dimeric receptor induces degranulation [17]. PAF also increases production of LTC 4 , and induces eosinophil release of multiple cytokines including interleukin 13 (IL-13), eotaxin-1, basic fibroblast growth factor, CCL5/RANTES, and platelet-derived growth factor (PDGF) [18].…”

“…In allergic rhinitis, rhinorrhea and mucous secretion are associated with the increased vascular permeability caused by PAF. In addition, PAF promotes the rapid translocation of inflammatory cells into nasal tissues [17]. …”

“…In contrast, rupatadine, a dual second-generation H1 antihistamine and PAFR blocker has proven clinically efficacious in urticaria, allergic rhinitis, and rhinoconjunctivitis [17, 27]. Randomized trials comparing rupatadine and levocetirizine demonstrate that rupatadine is better tolerated and more effective for chronic urticaria (Table 1) [41, 42].…”

Effects of Rupatadine on Platelet- Activating Factor–Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

“…Furthermore, PAF has been considered the most potent inducer of vascular permeability among the mediators involved in nasal inflammation, with a key role in rhinorrhea and nasal congestion [3,[8][9][10][11]. Finally, PAF levels and, more interestingly, PAF acetylhydrolase activity have been related to the severity of anaphylaxis [4,12].…”

“…It has the properties of an ideal second-generation antihistamine, including antiallergic/antiinflammatory effects such as inhibition of cytokine secretion [8,17]. In addition, the antagonistic effect of rupatadine on the PAF receptor has been demonstrated in in vitro studies and in a wide series of in vivo pharmacological studies based on both animals and humans [18].…”