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 Table of Contents  
Year : 2022  |  Volume : 8  |  Issue : 2  |  Page : 55-58

Bilastine up-dosing in chronic urticaria: A review

1 Department of Dermatology, Dr. DY Patil Medical College, Nerul, Navi Mumbai Maharashtra, India
2 Department of Dermatology, Apollo Hospital, Chennai, India
3 Department of Dermatology, BJ Medical College, Ahmedabad, Gujarat, India
4 Department of Dermatology, Max Super Speciality Hospital, New Delhi, India
5 Department of Dermatology, Krupa Shankar Skin Care Center, Mallige Hospital, Bengaluru, Karnataka, India
6 Department of Dermatology, Skin Diseases Center, Nashik, India
7 Department of Dermatology, Calcutta National Medical College, Kolkata, West Bengal, India
8 Department of Dermatology, The Medicity, Medanta Hospital, Gurugram, Haryana, India
9 Department of Dermatology, Hinduja Hospital, Mumbai, India
10 Department of Pharmacology, Dr. DY Patil Medical College, Nerul, Navi Mumbai, Maharashtra, India

Date of Submission07-Jul-2021
Date of Acceptance22-Dec-2022
Date of Web Publication5-Jan-2023

Correspondence Address:
Kiran Godse
Department of Dermatology, Dr. DY Patil Medical College, Nerul, Navi Mumbai Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijdd.ijdd_30_21

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Chronic urticaria, a heterogenous skin condition can be difficult to treat in many patients. It can adversely affect patient’s quality of life. Bilastine is a useful armamentarium for the management of chronic urticaria. This second generation H1 antihistamine is distinguished from most of its counterparts. Non-sedating potential, fast onset and longer duration of action, less risk of drug interactions and once daily administration make it an attractive option for use. In patients with chronic urticaria, not showing satisfactory response to standard doses, its dose can be increased up to four fold. In this review, we discuss the evidence of higher dose of bilastine in chronic urticaria and its place in therapy.

Keywords: Compliance, H1 antihistamine, higher dose, urticaria

How to cite this article:
Godse K, Rajagopalan M, Shah B, Girdhar M, Shankar K, Zawar V, De A, Sharma N, Tahiliani S, Patil A. Bilastine up-dosing in chronic urticaria: A review. Indian J Drugs Dermatol 2022;8:55-8

How to cite this URL:
Godse K, Rajagopalan M, Shah B, Girdhar M, Shankar K, Zawar V, De A, Sharma N, Tahiliani S, Patil A. Bilastine up-dosing in chronic urticaria: A review. Indian J Drugs Dermatol [serial online] 2022 [cited 2023 May 28];8:55-8. Available from: https://www.ijdd.in/text.asp?2022/8/2/55/367123

  Introduction Top

Chronic urticaria is a common heterogeneous skin disease all over the world. Chronic spontaneous urticaria (CSU) is associated with appearance of wheals, angioedema, or both for > 6 weeks. CSU affects up to 1% of the population. The condition is known to have an adverse bearing on the quality of life. The condition may persist for several years.

Histamine released from the activated mast cells in skin is a key mediator in the pathogenesis of CSU. It mediates development of many symptoms including wheal, neurogenic flare and wheal in patients with urticaria. Considering this H1-antihistamines given as continuous treatment are important treatment options in patients with chronic urticaria.[1] Non-sedating second generation H1 antihistamines are recommended as the first-line symptomatic treatment for chronic urticaria.

  Bilastine: A promising non-sedating H1 antihistamine Top

Brain H1 receptor occupancy is considered useful parameter for correlating with clinical findings. Based on the brain H1 receptor occupancy, antihistamines are classified into three types; non-sedating, less-sedating and sedating H1 antihistamines. Drugs in these categories have less than 20%, 20–50% and more than 50% brain H1 receptor occupancy. Based on the H1 receptor occupancy in the brain, bilastine has been classified as non-brain penetrating antihistamine.[2] Because of the high affinity for P-glycoprotein efflux pump, penetration of bilastine through blood brain barrier is restricted.[2],[3] Other factors such as molecular weight and electric charge are also contribute to the non-sedative potential and blood brain barrier penetration.[2]

In addition to non-sedative nature, it offers several other advantages including potent H1 receptor binding affinity and long lasting action.[2] No effect on psychomotor or driving performance even at 20 mg dose,[2] limited potential for drug-drug interactions,[4] makes it as one of the important armamentarium for use in actively working patient population.

Bilastine is used as one of the first line therapies in adults with chronic urticaria. It is given in the dose of 20 mg once daily. Generally, no laboratory tests are performed before its initiation with normal dose. It is advised to be taken one hour before or two hours after food or fruit juice.[5] Course of condition and response by the patient influences the duration of treatment.[6]

Its usage should be avoided with P-glycoprotein inhibitors in patients with moderate or severe renal impairment. It should also be avoided in patients with a history of QTc prolongation, torsade de pointes or those with known hypersensitivity to it. In otherwise healthy patients, not getting adequate control with normal dose, dose can safely be increased up to four fold. Considering absence of sufficient evidence, its usage in pregnancy should be avoided.[5] It is unknown if it is excreted in the human breast milk,[5] hence decision to use in lactating mothers should be taken based on risk and benefit ratio.[6] Once daily administration, no need for dose adjustment in liver or kidney impairment[2] are other benefits for its usage in clinical practice.

  Long Term Use of Bilastine Top

An open-label, multicentre study reported effects of bilastine 20 mg once a day in CSU or pruritus associated with dermatological conditions given up to 52 weeks. In this study, out of 198 patients enrolled, 122 (61.6%) completed the study. Bilastine improved disease symptoms early, and the efficacy was maintained during the study period. Study drug related adverse events were reported only in 2.5% of the patients. Importantly, none of the adverse event was serious.[7]

  Pharmacokinetics of Bilastine with Higher Dose Top

A single-blind, randomized study evaluated pharmacokinetics and pharmacodynamics of single- and multiple doses. In part I, bilastine was administered as single dose of 10, 20, and 50 mg whereas in part II it was given as once daily for 2 weeks at the dose of 20 and 50 mg. Single oral dose administration achieved maximum plasma concentrations at 1.0-1.5 hour after the dose. At single dose from 10-50 mg, the plasma exposure increased dose-proportionally. There was no considerable difference in plasma exposure at day 1 and day 14. As compared to placebo, wheal and flare inhibition with 20 and 50 mg was significant from 1.5 hours. The significant effect was persistent for 24 hours post-dose. No significant difference in the rates of adverse events was observed between bilastine and placebo in both parts of the study. No dose dependent tendency for rise in the incidence of adverse event was reported.[8]

  Evidence with Different Doses of Bilastine in Chronic Urticaria Top

Some retrospective studies have reported effectiveness and tolerability of bilastine in Indian patients not responding satisfactorily to other second generation antihistamines.[9],[10] A retrospective study has showed effectiveness of bilastine 20 mg in patients not responding to normal dose of levocetirizine. In this study, out of 230 patients, 169 (73.48%) were classified as responders and 19 (8.26%) reported adverse events. All of these adverse events were mild and no patient required discontinuation of treatment.[10]

A randomized, non-inferiority, multi-center open label study is being planned in Japan. The study is evaluating comparative efficacy of bilastine 20 mg versus double dose of H1-antihistamine in unresponsive patients with CSU to the standard dose of H1-antihistamine.[1]

Another retrospective study involving 49 adult patients with CSU with unsatisfactory response to previous antihistamine were switched over to bilastine 40 mg/day and continued it for 6 months in varying doses depending on the response. Complete response was reported in 25 (51%) patients after 24 weeks. In remaining 24 (49%) of patients urticaria was well-controlled. At 24 weeks, there was significant improvement in mean UAS7 score and mean DLQI score compared to baseline. In this study, patients with unsatisfactory response to other antihistamines at a double dose or combined use were also included.[9]

An open-label study reported effectiveness of bilastine at three doses (20, 40 and 80 mg) administered every day for 14 days in 29 patients with CSU who did provide satisfactory response to the normal doses of other H1-antihistamines. Bilastine 20 mg was an effective in relieving the symptoms in patients who did not respond to normal doses of H1-antihistamines. Up-dosing to 40 mg was effective in majority of patients. Only few patients i.e. those with more condition benefit from a fourfold dose.[11]

A small study from India (n=30) evaluated outcomes with bilastine in higher than usual doses in CSU with pruritus and wheal score of more than two. Patients were started with 20 mg dose given before breakfast. In patients without satisfactory response, dose of bilastine was increased to 40 mg at the end of one week. If the response was not satisfactory with 40 mg, dose was increased to 80 mg at the end of two weeks. Efficacy was evaluated with urticaria activity score and tolerability was assessed with sedation score. In this study, 30 patients with mean age 30.5 years with mean UAS of 5.2 were included. Data of 27 patients were available for evaluation. Symptom freedom was observed in 14 (51.85%) with bilastine 20 mg. Out of remaining 13 patients, 10 responded to 40 mg and 2 patients responded to 80 mg. Only 1 patient did not respond to bilastine 80 mg. There was no serious adverse event in any patient.[12]

Both these studies were conducted in patients with CSU but are associated with limitations of small sample size and no control group.[11],[12] One study with bilastine up-dosing in cold contact urticaria is also published. Krause and colleagues have published results of a randomized, crossover, double-blind, placebo-controlled 12 week study among 20 patients with cold contact urticaria. In this study, patients were given placebo, bilastine 20, bilastine 40 or bilastine 80 mg for one week with 14-day washout periods. Change in critical temperature thresholds (CTT) was the primary outcome measure. Symptom relief and levels of inflammatory markers collected by skin microdialysis and safety are also reported in this study. The study results showed effectiveness of bilastine 20 mg in reducing CTT. Bilastine 80 mg dose was associated with significant increase in effectiveness. Bilastine 80 mg was effective in 19 (95%) patients. Symptom freedom was achieved in 12 (60%) patients. After up-dosing with 80 mg, there was significant decrease in microdialysis levels of histamine, IL-6 and IL-8 assessed 1–3 h after cold challenge. Bilastine was well tolerated by the study participants without increased sedation with increased dose.[13] Available limited evidence is promising and supports effectiveness of bilastine in reducing the symptoms of CSU and cold contact urticaria.[13] These data supports the recommendations from urticaria treatment guidelines.[14]

  Guideline Recommendations in Chronic Urticaria Top

Guideline recommends up-dosing up to four fold in patients with chronic urticaria who do not respond to standard dose of second generation of antihistamine.[14] As, it is not deliberated in the guideline, at the moment the timing for administration of up-dosed quantity remains unclear. Clinical experience and interactions with experts in the management of chronic urticaria suggest that some clinicians give the up-dosed treatment with second generation H1 antihistamine in two divided doses whereas others give it at one time. Rationale for these two different approaches remains unknown. Most of the second generation H1 antihistamines can be given once a day. Studies have shown beneficial clinical effects of up-dosing with second generation H1-antihistamines, however, basic research to show effects on receptor occupancy and other inflammatory mediators is essential.

Promising pharmacological profile of bilastine in standard dose and the limited available published evidence with up-dosing with bilastine suggests that there is need for bilastine 40 mg tablet.

  Current Status of Bilastine 40 mg Tablet Top

As of now, there is limited evidence on bilastine 40 mg; Possibly suitable patients in whom bilastine 40 mg tablets will be useful are shown in [Table 1].
Table 1: Patients in whom bilastine 40 mg tablets may be useful

Click here to view

  Conclusion Top

Bilastine is a non-sedative antihistamine useful for treatment of patients with CSU. Bilastine given in the dose of 20 mg once daily is effective and well tolerated in patients with CSU. In retrospective studies, it has been shown to be effective in patients with CSU who did not respond satisfactorily to other second generation antihistamines. Bilastine in higher dose has been shown to be effective and well tolerated in patients who do not respond to normal dose.

Financial Support and Sponsorship


Conflicts of Interest

There are no conflicts of interest.

  References Top

Fukunaga A, Oda Y, Washio K, Omori T, Kakei Y, Hide M, et al. Efficacy of switching to bilastine, a histamine H1 receptor antagonist, in patients with chronic spontaneous urticaria (H1-SWITCH): Study protocol for a randomized controlled trial. Trials [Internet] 2020;21:23. Available from: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3878-2  Back to cited text no. 1
Kawauchi H, Yanai K, Wang DY, Itahashi K, Okubo K Antihistamines for allergic rhinitis treatment from the viewpoint of nonsedative properties. Int J Mol Sci2019;20:213.  Back to cited text no. 2
Wang XY, Lim-Jurado M, Prepageran N, Tantilipikorn P, Wang DY Treatment of allergic rhinitis and urticaria: A review of the newest antihistamine drug bilastine. Treatment of allergic rhinitis and urticaria: A review of the newest antihistamine drug bilastine. Therapeutics and Clinical Risk Management 2016;12:585-97.  Back to cited text no. 3
Church MK, Tiongco-Recto M, Ridolo E, Novák ZB A lifetime companion for the treatment of allergies. Curr Med Res Opin 2020;36:445-54. Available from: https://doi.org/10.1080/03007995.2019.1681134. [Internet].  Back to cited text no. 4
Gandhi J, Godse K, Godse GB A novel antihistamine. Indian J Drugs Dermatology 2018;4:3.  Back to cited text no. 5
Godse K, De A, Zawar V, Shah B, Girdhar M Bilastine for the treatment of chronic spontaneous urticaria: Consensus statement for Indian patients. IP Indian J Clin Exp Dermatology 2021;5:180-5.  Back to cited text no. 6
Yagami A, Furue M, Togawa M, Saito A, Hide M One-year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases. J Dermatol 2017;44:375-85.  Back to cited text no. 7
Togawa M, Yamaya H, Rodríguez M, Nagashima H Pharmacokinetics, pharmacodynamics and population pharmacokinetic/pharmacodynamic modelling of bilastine, a second-generation antihistamine, in healthy japanese subjects. Clin Drug Investig 2016;36:1011-21.  Back to cited text no. 8
De A, Godse K, Dhoot D, Sarda A Real-life experience of efficacy and safety of bilastine in refractory cases of chronic spontaneous urticaria and its effect on the quality of life of patients. Indian J Dermatol 2021;66:159-64.  Back to cited text no. 9
Shah B, De A, Sarda A, Kocchar AM, Dhoot D, Deshmukh G, et al. Effect of bilastine on chronic spontaneous urticaria refractory to levocetirizine: Real world experience in India. Dermatol Therapy 2021;34:e14557.  Back to cited text no. 10
Weller K, Church MK, Hawro T, Altrichter S, Labeaga L, Magerl M, et al. Updosing of bilastine is effective in moderate to severe chronic spontaneous urticaria: A real-life study. Allergy Eur J Allergy Clin Immunol 2018;7310:2073-5.  Back to cited text no. 11
Godse K Bilastine in higher dose in chronic spontaneous urticaria in higher doses. IP Indian J Clinical Exper Dermatol 2019;5: 261-3.  Back to cited text no. 12
Krause K, Spohr A, Zuberbier T, Church MK, Maurer M Up-dosing with bilastine results in improved effectiveness in cold contact urticaria. Allergy Eur J Allergy Clin Immunol 2013;687:921-8.  Back to cited text no. 13
Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Ballmer-Weber B, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy Eur J Allergy Clin Immunol 2018;73:1393-414.  Back to cited text no. 14


  [Table 1]


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