Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine

Abstract

Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug-drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug's safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria.

Keywords: allergic rhinitis; bilastine; second-generation antihistamines; urticaria.

Figure 1

Intracellular signaling processes mediated by G-proteins after interaction of histamine with each receptor subtype. Abbreviations: AC, adenylate cyclase; Akt, protein kinase B; cAMP, cyclic adenosine monophosphate; CREB, cAMP response element-binding protein; DAG, diacyl glycerol; IP₃, inositol triphosphate; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C.

Figure 2

Direct downregulation of allergic inflammation by H₁ antihistamines.

Figure 3

Chemical structure of bilastine.

Figure 4

Affinity of bilastine to human H₁ receptors expressed in HEK-293 cell. Note: Reproduced from Drugs R D, A Preclinical pharmacology of bilastine, a new selective histamine H₁ receptor antagonist: receptor selectivity and in vitro antihistaminic activity, 2005;6:371–384, Corcostegui R, Labeaga L, Innerarity A, Berisa A, Orjales A, Copyright ©2005, With permission of Springer.

Figure 5

Predicted and observed plasma concentration–time profile after oral administration of a single 20 mg dose of bilastine to healthy volunteers. Note: Reproduced from Clin Pharmacokinet, Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine, 2009;48:543–554, Jauregizar N, de la Fuente L, Lucero ML, Sologuren A, Leal N, Rodríguez M, Copyright ©2009, With permission of Springer. Abbreviation: h, hours.

Figure 6

Percentage decrease from baseline in NSS and NNSS in a randomized, double-blind, placebo-controlled study of bilastine versus cetirizine in patients with seasonal allergic rhinitis. Note: *P<0.001 versus placebo. Data from Kuna et al. Abbreviations: NSS, nasal symptom score; NNSS, nonnasal symptom score.

Figure 7

Effects of three antihistamines on TNSS in a Vienna Challenge Chamber study performed in 75 individuals with asymptomatic seasonal allergic rhinitis. Notes: *P<0.001 versus placebo, ^#P=0.0012 for bilastine versus fexofenadine, ^&P<0.001 for cetirizine versus fexofenadine. Data from Horak et al. Abbreviation: TNSS, total nasal symptom score.

Figure 8

Mean decreases in TSS during 4 weeks’ administration of bilastine or levocetirizine to patients with chronic spontaneous urticaria. Notes: *P<0.001 versus placebo. Reproduced from Zuberbier T, Oanta A, Bogacka E, et al; Bilastine International Working Group. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy. 2010;65:516–528. With permission from John Wiley and Sons. Copyright ©2009. Abbreviation: TSS, total symptom score.

Figure 9

Efficacy of increased dosages of second-generation antihistamines in chronic urticaria. Note: Adapted from Sanchez-Borges M, Ansotegui I, Jimenez JM, Rojo MI, Serrano C, Yañez A. Comparative efficacy of non-sedating antihistamine updosing in patients with chronic urticaria. World Allergy Organ J. 2014;7:33.