Биластин 20 мг инструкция по применению цена отзывы

• 39k Accesses

• 35 Citations

• 12 Altmetric

• Metrics details

Bilastine is a new second generation H1-antihistamine recently approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU) in patients older than 12 years of age. AR and urticaria are very common clinical conditions that represent one of the most frequent reasons for a patient to visit their general practitioner or allergist. In the European countries 18% of population is suffering from AR [1] and in the United States AR affects a range of 10-30% of adults and up to 40% of children [2]. For urticaria, the life-time prevalence is approximately 20% for acute urticaria and 1.8% for CU [3]. These two clinical entities, though they have different and distinct characteristics, both cause a significant impairment of quality of life (QoL) and loss of productivity [4-6]. AR and urticaria respond to antihistamine treatment and current international guidelines recommend nonsedating second generation antihistamines as first line treatment for both [3,7,8].

The role of histamine in allergic inflammation is unequivocal. It exerts its biological effects acting on four distinct receptors, but among them the H1-receptor plays the most important role in allergic diseases. H1-antihistamines can control allergic inflammation by directly interfering with histamine action at H1 receptors [9]. Based on their ability to cross the blood–brain barrier, H1-antihistamines are classified into 2 groups: the first generation antihistamines that bind the H1-receptors on neurons in the central nervous system, causing sedation and impaired mental status, and the second-generation antihistamines (including bilastine) that usually cannot cross the blood–brain barrier and thus have fewer sedative effects. The long duration of action, efficacy, low-sedation impact and low-performance impairment of second generation antihistamines, and particularly of bilastine, make it a potentially attractive therapeutic option for allergists.

This review focuses on the clinical characteristics of bilastine and the evidence of its efficacy in the treatment of AR and urticaria.

Pharmacodynamic and pharmacokinetic properties

From a molecular point of view, bilastine is 2-[4-(2-(4-(1-(2- ethoxyethyl)-1Hbenzimidazol-2-yl) piperidin-1-yl) ethyl) phenyl]-2-methyl propionic acid. It belongs to piperidine derivatives and is not structurally derived from any other currently available antihistamines. Bilastine exerts a potent and specific H1-antihistamine activity.

Bilastine is an H1 receptor inverse agonist, like other antihistamines already available. Preclinical in vitro studies showed that bilastine has high specificity for H1-receptors while has negligible affinity for 30 other receptors (serotonin, bradykinin, leukotriene-D4, muscarinic M3-receptors, α1-adrenoceptors, β2-adrenoceptors, and H2- and H3-histamine receptors) [10]. The affinity for the H1 receptor is 3 and 6 times higher than for cetirizine and fexofenadine, respectively. The results of in vivo preclinical studies confirmed those obtained from in vitro experiments, as in rats bilastine has demonstrated to reduce histamine-stimulated smooth muscular contraction, bronchospasms, endothelial permeability, and microvascular extravasation, providing evidence to possess antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine [11].

In vitro data have shown that bilastine also exerts anti-inflammatory activity by inhibiting the release of histamine, IL-4 and tumor necrosis factor (TNF)-α from human mast cells and granulocytes [12].

The drug is rapidly absorbed after oral administration with a time to maximum plasma concentration of around 1 hour following administration [13]. The mean value of bilastine oral bioavailability was found to be about 60% [14]. The maximum plasma concentration (220 ng/mL) of bilastine 20 mg was detected 1.3 hours after administration, the half time was 14.5 hours, and plasma protein binding was 84–90% [13,14]. Bilastine does not undergo any significant hepatic metabolism and approximately 95% is excreted intact in faeces (67%) or in urine (33%); bilastine is a substrate for P-glycoprotein which limits its passage across the blood–brain barrier [15], and not clinically relevant interactions have been reported to date. The mean elimination half-life calculated in healthy volunteers was 14.5 h and the apparent total plasma clearance is 18.1 L/h [16,17]. Bilastine is not a substrate of CYP450 family [18].

Efficacy of bilastine

Wheal and flare inhibition

A phase 1, double-blind, randomised, placebo-controlled, single oral dose, cross-over study compared the antihistaminic effects of bilastine, cetirizine and placebo against histamine-induced wheal and flare responses, over periods of 24 h, in 21 healthy male volunteers [19]. In that trial, volunteers were randomised to receive single oral doses of bilastine 20 or 50 mg, cetirizine 10 mg or placebo before provocation of wheal and flare responses to 100 mg/ml histamine by skin prick 1.5, 4, 8, 12 and 24 h later. The authors found no significant differences between overall inhibitions of wheal or flare by bilastine 20 mg and cetirizine10 mg but bilastine was faster in onset of action than cetirizine, inhibition of wheal and flare at 1.5 h being 89 ± 3 versus 44 ± 14% (P = 0.011) and 85 ± 4 versus 45 ± 14% (P = 0.016), respectively. At 1.5 h, both wheals and flares were inhibited by 70% in 11/12 volunteers taking bilastine and 3/11 taking cetirizine (P = 0.003). There were no significant differences between the drugs at later times.

Bilastine efficacy in allergic rhinitis

Efficacy of bilastine was well recognized in both seasonal and perennial allergic rhinitis. The Vienna Challenge Chamber is an established standardized method for the controlled exposure of patients to defined allergens, that is used to make comparisons between different antihistamines [20,21]. Using this method, a double blind, randomized, placebo controlled, balanced four-treatment, four-period crossover phase II study was conducted in patients suffering from seasonal AR (SAR) in order to compare the efficacy of bilastine, cetirizine and fexofenadine to relieve symptoms [22]. The study was conducted in adult patients with confirmed allergy to grass pollen, outside the pollen season while they were asymptomatic. Total Nasal Symptoms Score (TNSS) was used to compare the effect of a single dose of bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg and placebo administered two hours after the start of the challenge. During the first four hours after administration, all treatment were significantly more effective than placebo in reducing TNSS (p < 0.001), without significant difference between the three antihistamines. Moreover, bilastine at 20 mg was as effective as cetirizine 10 mg and fexofenadine 120 mg in terms of onset of action and in reducing eye symptoms 1 h after the intake. Bilastine was still effective 26 hours after the intake, confirming the prolonged duration of action.

The efficacy of bilastine in patients with SAR has also been evaluated in two double-blind, placebo-controlled studies, with the same design, evaluating parameters for efficacy and safety, including assessment of QoL in the first one, comparing once daily bilastine 20 mg with placebo, desloratadine 5 mg and cetirizine 10 mg over two weeks [23,24]. Details of the two studies are provided in table 1. These two studies enrolled a total of 1404 patients, aged between 12 and 70 years, with documented SAR due to pollen allergens. In both studies primary outcome measure of TSS was significantly reduced in the bilastine group significantly more than in the placebo group and to a similar extent as in the active comparator group (table 1). Also, bilastine improved QoL, measured by rhinoconjunctivitis quality of life questionnaire (RQLQ), to a similar extent than desloratadine; bilastine 20 mg significantly improved total RQLQ score and most RQLQ single domains respect to placebo.

A multicenter, randomized, placebo-controlled, double-blind, parallel-group study was conducted in 650 patients with symptomatic persistent AR (PAR) [25]. The authors found no significant differences in efficacy outcomes between active treatments and placebo in the overall population, over 4 weeks of treatment, but in the post-hoc analysis bilastine 20 mg was more effective than placebo and as effective as cetirizine 10 mg the population of patients from Europe and Argentina, while the difference remained not statistically significant in patients from South Africa. The lack of efficacy through the whole group was likely to be due to the group great variability of symptom scores reported in different countries, particularly in South Africa [26].

Davila et al. and Bartra et al. analyzed the data about the effect of bilastine upon nasal obstruction and ocular symptoms from 7 phase II and phase III 2–4 weeks duration clinical trials [27,28]. Mean change from baseline in nasal obstruction symptoms score after two weeks of treatment was −0.66 with bilastine 20 mg and −0.57 with placebo (p < 0.001), active comparators (cetirizine 10 mg and desloratadine 5 mg) induced a reduction of −0.67 points (p < 0.001 vs placebo; not statistically different vs bilastine) [27]. Similarly, bilastine was more effective in ocular symptoms relief than placebo and as effective as active comparators [28].

Bilastine efficacy in urticaria

A multi-centre, double-blind, randomized, placebo-controlled study compared the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria in 525 adult patients [29]. The TSS was reduced progressively by all treatments from baseline over a period of 28 days treatment, with significant differences noted between bilastine 20 mg and levocetirizine 5 mg-treated groups vs placebo-treated group from day 2 onward over the entire treatment period . The mean change from baseline in the patients’ reflective daily TSS over the 28-day treatment period, that was the primary efficacy measure, was significantly greater for bilastine 20 mg and levocetirizine 5 mg treated groups compared with placebo-treated group (P < 0.001 for bilastine and levocetirizine vs placebo), but not significantly different between the active treatment groups.

Cold urticaria is a quite uncommon form of inducible urticaria, characterized by pruritic wheals and/or angioedema due to cutaneous mast cell activation and release of pro-inflammatory mediators after cold exposure [30]. Reduction of symptoms in many patients with cold urticaria requires high dosing with antihistamines, up to four times the daily recommended dose [31,32]. Krause et al. assessed the effects of the standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CU and inflammatory mediator release following cold challenge in a randomized, crossover, double-blind, placebo-controlled 12-week study [33]. In this study patients suffering from cold urticaria, confirmed by a specific provocation test, received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. Bilastine was effective already at routine doses: in patients receiving 20 mg, the critical temperature threshold (CCT, the highest temperature that produces a positive wheal response) was significantly different from placebo (the median CCT value was 6°C in bilastine group and 18°C in placebo group), P < 0.0001), as well as the number of patients that became symptom free (P = 0.044). The up-dosing was beneficial, since the median CTT with bilastine 80 mg was significantly lower than that of 20 mg (P = 0.003) and 40 mg (P = 0.04). Moreover, inflammatory mediators were significantly reduce by bilastine 80 mg.

Safety of bilastine

Tolerability data from the four phase III trials of 2–4 weeks duration are summarized in table 2. In these studies, bilastine was well tolerated and the majority of the adverse events described were either mild or moderate, while no serious adverse events or death were reported; moreover, there were no clinically significant changes in any laboratory tests, ECGs, heart rate, or systolic and diastolic blood pressure, in patients treated with bilastine 20 mg. The most common adverse effects were headache, somnolence and fatigue that were reported less frequently than in patients receiving cetirizine at 10 mg once daily. The frequency of these adverse effects in patients with SAR were comparable with that of desloratadine. The first generation antihistamines cross the blood–brain barrier and bind the H1-receptors on postsynaptic neurons membranes in the central nervous system, causing sedation and impaired mental status, while the second-generation antihistamines usually do not cross the blood–brain barrier and have fewer sedative effects. Bilastine 20 mg histamine H1-receptor occupancy had been evaluated by positron emission tomography (PET) in healthy subjects, confirming that bilastine has objective and PET criteria to be defined as a non-sedating antihistamine [34]. Moreover, bilastine demonstrated to produce only very little or even no performance impairment. In a crossover, randomized, double-blind, placebo-controlled study 20 healthy volunteers received repeated doses of bilastine 20, 40, or 80 mg and first generation antihistamine hydroxyzine 25 mg on 7 consecutive days [35]. Bilastine in doses up to 40 mg did not produce psychomotor impairment as compared with placebo, even if 40 mg produced subjective report of sedation, and an objective impairment was only evident at bilastine doses of 80 mg. Similarly, bilastine did not produce any driving impairment after single and repeated doses up to 40 mg [36]. At the therapeutic dose of 20 mg the concomitant administration of bilastine and alcohol does not produce greater central nervous system (CNS) depressant effects than alcohol alone, while objective impairment induced bilastine 80 mg + alcohol (0.8 g/Kg) was of similar magnitude to that induced by hydroxyzine 25 mg + alcohol [37]. Also cardiac safety was confirmed at therapeutic and supra-therapeutic doses. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc. Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc but this result was most likely related to the cardiac effect of ketoconazole [38]. Moreover, bilastine, at therapeutic and supratherapeutic dosages (up to 100 mg), did not induce any effects on T-wave morphology [39].

1. Bousquet J, Van Cauwenberge P, Khaltaev N, ARIA Workshop Group. World health organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108(5 Suppl):S147–334.

   Article 
   CAS 
   PubMed 

   Google Scholar 

2. Dykewicz MS, Fineman S. Executive summary of joint task force practice parameters on diagnosis and management of rhinitis. Ann Allergy Asthma Immunol. 1998;81:463–8.

   Article 
   CAS 
   PubMed 

   Google Scholar 

3. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA (2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69(7):868–87.

   Article 
   CAS 
   PubMed 

   Google Scholar 

4. Kakumanu S, Glass C, Craig T. Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal congestion. Am J Respir Med. 2002;1(3):195–200.

   Article 
   PubMed 

   Google Scholar 

5. Thompson AK, Juniper E, Meltzer EO. Quality of life in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2000;85:338–47.

   Article 
   CAS 
   PubMed 

   Google Scholar 

6. Weldon D. Quality of life in patients with urticaria and angioedema: assessing burden of disease. Allergy Asthma Proc. 2014;35(1):4–9.

   Article 
   PubMed 

   Google Scholar 

7. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update. Allergy. 2008;63 Suppl 86:8–160.

   Article 
   PubMed 

   Google Scholar 

8. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011;106(2Suppl):S12–6.

   Article 
   PubMed 

   Google Scholar 

9. Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011;128(6):1139–1150.e4.

   Article 
   CAS 
   PubMed 

   Google Scholar 

10. Corcóstegui R, Labeaga L, Innerárity A, Berisa A, Orjales A. Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity. Drugs R D. 2005;6(6):371–84.

    Article 
    PubMed 

    Google Scholar 

11. Corcóstegui R, Labeaga L, Innerárity A, Berisa A, Orjales A. In vivo pharmacological characterisation of bilastine, a potent and selective histamine H1 receptor antagonist. Drugs R D. 2006;7(4):219–31.

    Article 
    PubMed 

    Google Scholar 

12. Alvarez-Mon M, San Antonio E, Lucero M, Sanz E, Ledo F, De la Hera A. Bilastine, a novel antihistamine that preferentially inhibits histamine and interleukin-4 release from human mast cells and granulocytes. Allergy. 2009;64 Suppl 90:555.

    Google Scholar 

13. Jauregizar N, de la Fuente L, Lucero ML, Sologuren A, Leal N, Rodríguez M. Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine. Clin Pharmacokinet. 2009;48(8):543–54.

    Article 
    CAS 
    PubMed 

    Google Scholar 

14. Sádaba B, Gómez-Guiu A, Azanza JR, Ortega I, Valiente R. Oral availability of bilastine. Clin Drug Investig. 2013;33(5):375–81.

    Article 
    PubMed 

    Google Scholar 

15. Lucero ML, Gonzalo A, Ganza A, Leal N, Soengas I, Ioja E, et al. Interactions of bilastine, a new oral H (1) antihistamine, with human transporter systems. Drug Chem Toxicol. 2012;35 Suppl 1:8–17.

    Article 
    CAS 
    PubMed 

    Google Scholar 

16. Lucero ML, Gonzalo A, Mumford R, Betanzos M, Alejandro A. An overview of bilastine metabolism during preclinical investigations. Drug Chem Toxicol. 2012;35 Suppl 1:18–24.

    Article 
    CAS 
    PubMed 

    Google Scholar 

17. Sologuren A, Lucero ML, Valiente R, Valiente R, Charles H, Mair SJ. Human mass balance with [14C]-bilastine following oral administration to healthy volunteers. Basic Clin Pharmacol Toxicol. 2009;105 Suppl 1:106–7.

    Google Scholar 

18. Lucero ML, Orjales A, Morag N. In vitro hepatic metabolism of [14C]-bilastine. suppl I. 2007;39:114.

    Google Scholar 

19. Church MK. Comparative inhibition by bilastine and cetirizine of histamine-induced wheal and flare responses in humans. Inflamm Res. 2011;60(12):1107–12.

    Article 
    CAS 
    PubMed 

    Google Scholar 

20. Horak F, Jager S. Wiener Provokations-Kammer (Vienna challenge chamber): eine neue Methode des Allergenexpositionstests. Wiener klin Wochenschr. 1987;99:509–10.

    Google Scholar 

21. Stübner P, Zieglmayer R, Horak F. A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit — the Vienna challenge chamber (VCC). Curr Med Res Opin. 2004;20(6):891–902.

    Article 
    PubMed 

    Google Scholar 

22. Horak F, Zieglmayer P, Zieglmayer R, Lemell P. The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna challenge chamber. Inflamm Res. 2010;59(5):391–8.

    Article 
    CAS 
    PubMed 

    Google Scholar 

23. Bachert C, Kuna P, Sanquer F, Ivan P, Dimitrov V, Gorina MM, et al. Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patients. Allergy. 2009;64:158–65.

    Article 
    CAS 
    PubMed 

    Google Scholar 

24. Kuna P, Bachert C, Nowacki Z, van Cauwenberge P, Agache I, Fouquert L, et al. Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: A randomized, double-blind, parallelgroup study. Clin Exp Allergy. 2009;39:1338–47.

    Article 
    CAS 
    PubMed 

    Google Scholar 

25. Sastre J, Mullol J, Valero A, Valiente R, Bilastine Study Group. Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis. Curr Med Res Opin. 2012;28(1):121–30.

    Article 
    CAS 
    PubMed 

    Google Scholar 

26. Kowal K, DuBuske L. Bilastine as a potential treatment in allergic rhinitis. Am J Rhinol Allergy. 2014;28(4):312–6.

    Article 
    PubMed 

    Google Scholar 

27. Dávila I, Sastre J, Mullol J, Montoro J, Jáuregui I, Ferrer M, et al. Effect of bilastine upon nasal obstruction. J Investig Allergol Clin Immunol. 2011;21 Suppl 3:2–8.

    PubMed 

    Google Scholar 

28. Bartra J, Mullol J, Montoro J, Jáuregui I, del Cuvillos A, Dávila I, et al. Effect of bilastine upon the ocular symptoms of allergic rhinoconjunctivitis. J Investig Allergol Clin Immunol. 2011;21 Suppl 3:24–33.

    CAS 
    PubMed 

    Google Scholar 

29. Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, et al. 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(4):516–28.

    Article 
    CAS 
    PubMed 

    Google Scholar 

30. Siebenhaar F, Weller K, Mlynek A, Magerl M, Altrichter S, Vieira Dos Santos R, et al. Acquired cold urticaria: clinical picture and update on diagnosis and treatment. Clin Exp Dermatol. 2007;32(3):241–5.

    Article 
    CAS 
    PubMed 

    Google Scholar 

31. Magerl M, Pisarevskaja D, Staubach P, Martus P, Church MK, Maurer M. Critical temperature threshold measurement for cold urticaria: a randomized controlled trial of H (1) -antihistamine dose escalation. Br J Dermatol. 2012;166(5):1095.

    Article 
    CAS 
    PubMed 

    Google Scholar 

32. Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol. 2009;123(3):672.

    Article 
    CAS 
    PubMed 

    Google Scholar 

33. Krause K, Spohr A, Zuberbier T, Church MK, Maurer M. Up-dosing with bilastine results in improved effectiveness in cold contact urticaria. Allergy. 2013;68(7):921–8.

    Article 
    PubMed Central 
    CAS 
    PubMed 

    Google Scholar 

34. Farré M, Pérez-Mañá C, Papaseit E, Menoyo E, Pérez M, Martin S, et al. Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers. Br J Clin Pharmacol. 2014;78(5):970–80.

    Article 
    PubMed Central 
    PubMed 

    Google Scholar 

35. García-Gea C, Martínez-Colomer J, Antonijoan RM, Valiente R, Barbanoj MJ. Comparison of peripheral and central effects of single and repeated oral dose administrations of bilastine, a new H1 antihistamine: a dose-range study in healthy volunteers with hydroxyzine and placebo as control treatments. J Clin Psychopharmacol. 2008;28(6):675–85.

    Article 
    PubMed 

    Google Scholar 

36. Conen S, Theunissen EL, Van Oers AC, Valiente R, Ramaekers JG. Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers. J Psychopharmacol. 2011;25(11):1517–23.

    Article 
    CAS 
    PubMed 

    Google Scholar 

37. García-Gea C, Martínez J, Ballester MR, Gich I, Valiente R, Antonijoan RM. Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials. Hum Psychopharmacol. 2014;29(2):120–32.

    Article 
    PubMed 

    Google Scholar 

38. Tyl B, Kabbaj M, Azzam S, Sologuren A, Valiente R, Reinbolt E, et al. Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis. J Clin Pharmacol. 2012;52(6):893–903.

    Article 
    CAS 
    PubMed 

    Google Scholar 

39. Graff C, Struijk JJ, Kanters JK, Andersen MP, Toft E, Tyl B. Effects of bilastine on T-wave morphology and the QTc interval: a randomized, double-blind, placebo-controlled, thorough QTc study. Clin Drug Investig. 2012;32(5):339–51.

    Article 
    CAS 
    PubMed 

    Google Scholar 

40. Sadaba B, Azanza JR, Gomez-Guiu A, Rodil R. Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria. Ther Clin Risk Manag. 2013;9:197–205.

    Article 
    PubMed Central 
    CAS 
    PubMed 

    Google Scholar 

41. Bousquet J, Ansótegui I, Canonica GW, Zuberbier T, Baena-Cagnani CE, Bachert C, et al. Establishing the place in therapy of bilastine in the treatment of allergic rhinitis according to ARIA: evidence review. Curr Med Res Opin. 2012;28(1):131–9.

    Article 
    CAS 
    PubMed 

    Google Scholar 

42. Jauregui I, Ferrer M, Bartra J, del Cuvillo A, Davila I, Montoro J, et al. Bilastine for the treatment of urticaria. Expert Opin Pharmacother. 2013;14(11):1537–44.

    Article 
    CAS 
    PubMed 

    Google Scholar 

43. Scaglione F. Safety profile of bilastine: 2nd generation H1-antihistamines. Eur Rev Med Pharmacol Sci. 2012;16:1999–2005.

    CAS 
    PubMed 

    Google Scholar 

44. Zuberbier T. Pharmacological rationale for the treatment of chronic urticaria with second-generation non-sedating antihistamines at higher than standard doses. J Eur Acad Dermatol Venereol. 2012;26(1):9–18.

    Article 
    CAS 
    PubMed 

    Google Scholar 

Download references

Authors and Affiliations

1. Department of Clinical and Experimental Medicine, University of Parma, via Gramsci 14, Parma, 43126, Italy

   Erminia Ridolo, Marcello Montagni & Laura Bonzano

2. Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy

   Cristoforo Incorvaia

3. Allergy and Respiratory Diseases Clinic, DIMI, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy

   Giorgio Walter Canonica

Corresponding author

Correspondence to
Erminia Ridolo.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

All authors have contributed equally to the the writing of the manuscript. All authors read and approved the final manuscript.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions