Second-generation H1-antihistamines Research Articles

Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study

BackgroundBilastine, a novel non-sedating second-generation H1-antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18–74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day −3 to 0) in total symptom score (TSS) at 2 weeks (Day 8–14), consisting of the itch and rash scores. ResultsA total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. ConclusionsTwo-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action.

Rupatadine: global safety evaluation in allergic rhinitis and urticaria

ABSTRACTIntroduction: Rupatadine is a second-generation H1-antihistamine with dual affinity for histamine H1 and PAF receptors. Rupatadine is indicated for the treatment of allergic rhinitis and urticaria.Areas covered: A Medline search was conducted to identify preclinical and clinical studies of rupatadine. This was supplemented with additional articles obtained from online sources. The focus of this review is on the safety profile of rupatadine.Expert opinion: The review of these data indicates that rupatadine is highly selective for histamine H1-receptors, exhibits additional PAF antagonism in in vitro and in vivo studies, does not cross the blood-brain barrier, and has similar adverse events comparable with other second-generation antihistamines. Rupatadine is a safe and well tolerated drug in patients over 2 years old, with no central nervous system or cardiovascular effects and it can be taken with or without foods.

Therapeutic effect of bilastine in Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber)

BackgroundEnvironmental exposure chambers have been used to expose subjects to aeroallergens to investigate the efficacy of prophylactic treatment with symptomatic agents in Japan. We first examined the therapeutic effect of bilastine (BIL), a novel non-sedative second-generation H1-antihistamine, in subjects with Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber). MethodsThis was a randomized, double-blind, four-way crossover, placebo- and active-controlled phase II study (trial registration number JapicCTI-132213). Subjects were exposed to cedar pollen (8000 grains/m3) for 2 h on Day −1 and 4 h each on Day 1 and 2. BIL 10 or 20 mg, placebo, or fexofenadine hydrochloride (FEX) 60 mg was administered orally 1 h after the start of pollen exposure on Day 1. Placebo or FEX was administered 12 h after the first dosing. The primary efficacy endpoint was the sum of total nasal symptom score (TNSS) from 0 to 3 h after the Day 1 dosing. ResultsWe enrolled 136 subjects and the sum of TNSS on Day 1 of the three active treatments was significantly lower than that of placebo and was maintained up to 26 h after the first dosing (Day 2). The sum of TNSS or sneezing score on Day 1 after BIL 20 mg was more significantly decreased than after FEX. Moreover, BIL showed a faster onset of action than FEX. ConclusionsWe demonstrated the efficacy, rapid onset, and long duration of action of BIL in subjects with Japanese cedar pollinosis exposed to cedar pollen using the OHIO Chamber.

Allergic Rhinitis Control Test questionnaire-driven stepwise strategy to improve allergic rhinitis control: a prospective study.

Allergic Rhinitis Control Test (ARCT) has been validated for assessing allergic rhinitis (AR) control and identifying severe AR. The aim of the study was to assess the ARCT questionnaire as a tool for stepwise pharmacotherapy. A standard pharmacotherapy regimen from Step 1 (oral second-generation H1 antihistamine as needed) to Step 5 (oral corticosteroid) was carried out prospectively in a Chinese AR population. The AR patients were initiated with Allergic Rhinitis and its Impact on Asthma (ARIA) appropriate step treatment and assessed with ARCT every 15 days. If ARCT score was equal or above 20 (controlled AR) and maintained for 15 days, the patient would finish the study; if ARCT score was strictly <20 (uncontrolled AR), the patient would receive higher step treatment according to a predefined open design up to Step 5. The different AR control subgroups were compared. A total of 255 patients were enrolled in the study; 5 patients dropped out and 2 (0.8%) were controlled at day 0, 85 (34.0%) at day 15, 177 (70.8%) at day 30, 222 (88.8%) at day 45, 241 (96.4%) at day 60 and 242 (96.8%) at day 75. Only 8 (3.2%) patients remained uncontrolled at the endpoint of the study. Patients with ARIA moderate/severe or persistent symptoms, moderate/severe impaired quality of life, asthma history, rhinorrhea and cough symptoms always needed up to Step 4 (nasal corticosteroid plus antihistamine) and prolonged treatments to achieve disease control. The majority of AR can be controlled with standard stepwise treatment. ARCT offers an objective criterion for the stepwise pharmacotherapy of AR.

Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study

BackgroundBilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). MethodsThis randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10–13). ResultsA total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (−0.98) compared to placebo (−0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (−0.99) than by placebo (−0.28, P < 0.001) or fexofenadine (−0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. ConclusionsAfter 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

Recurrent and Persistent Urticaria: Is It Chronic Idiopathic Urticaria?

ABSTRACT Chronic idiopathic urticaria (CIU), defined as wheals and/or angioedema lasting for ≥6 weeks without an identifiable cause, is a burdensome condition. This review provides recommendations regarding the efficient recognition and differential diagnosis of CIU from other chronic urticaria forms and discusses the importance of evaluating CIU’s impact on patients’ quality of life and assessing unmet treatment needs. The goal of treatment is achieving complete resolution of symptoms through a systematic approach and close patient cooperation, thereby improving quality of life. The U.S. Practice Parameter describes a step-care approach to CIU management, with second-generation H1-antihistamines at approved doses as the first-line treatment. For patients with inadequately controlled symptoms, dose advancement or add-on therapies, followed by use of potent antihistamines, may be considered. Of the alternative agents available for the treatment of patients with refractory CIU, omalizumab, an anti-immunoglobulin E monoclonal antibody, is the only treatment approved by the Food and Drug Administration for use in adults and adolescents (≥12 years old) with CIU who remain symptomatic despite H1-antihistamine therapy. Ultimately, treatment decisions should weigh the potential clinical benefit versus harm for each agent and consider the patient’s preference. By discussing available treatment options and providing evidence-based recommendations, this review aims to support aspects of decision making when managing this complex condition.

Urticaria and angioedema.

Urticaria, also known as hives, may affect up to 20% of the population at some time. Urticaria is described as pruritic erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. Urticaria is closely associated with angioedema in 40% of individuals; approximately 10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized, with multiple lesions in no specific distribution; angioedema tends to be localized and commonly affects the face (periorbital and perioral regions) or tongue. Urticaria is subdivided into acute and chronic urticaria based on the duration of symptoms. Acute urticaria lasts < 6 weeks, and an identifiable cause, such as food products, medications (aspirin, nonsteroidal anti-inflammatory drugs, antibiotics), or insect stings, may be discovered. Urticaria that lasts for >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered spontaneous. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto disease) and urticaria and angioedema, with a higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these patients, who are usually euthyroid. Furthermore, results of studies revealed a circulating immunoglobulin G (IgG) antibody directed against the high affinity IgE receptor alpha subunit IgE receptor (FcεRI) or IgE in 40-60% of patients with chronic urticaria. A stepwise approach to the treatment of urticarial is recommended with second-generation H1 antihistamines being the first line of therapy.

Prescription analysis of both H1 and H2 antihistamines among in-patients of dermatology department of a tertiary care teaching hospital in a coastal town of South India

Background: Antihistamines are one of the commonly used drugs for treating dermatological disorders. Periodic evaluation of prescribing patterns can increase the therapeutic efficacy, decrease adverse effects, and provide feedback to prescribers. Aims and Objectives: The objective of the present study was to evaluate the prescribing pattern of both H1 and H2 antihistamines in in-patients of dermatology department in a tertiary care teaching hospital. Materials and Methods: A prospective observational study was carried out in the Department of Dermatology of Vinayaka Missions Medical College and Hospital, Karaikal. A total of 291 prescriptions belonging to in-patients of dermatology department were scrutinized during the study period. Patient’s age, sex, and pattern of skin diseases reported and trends in antihistaminic drug usage as monotherapy or as combinations were analyzed. Most common adverse effects of the prescribed antihistamines were graded, and data were expressed as absolute numbers and percentages. Results: Out of the total 291 prescriptions screened, 213 (73.2%) contained at least one antihistaminic drug. The majority of patients were in the age group of 41-50 years (26.83%) followed by 31-40 years (22.36%). Psoriasis, eczema, and allergic contact dermatitis were the top three disorders for which antihistamines were prescribed. Overall second-generation H1 antihistamines were prescribed more commonly than their first-generation counterparts. The most commonly prescribed antihistamine as monotherapy was cetirizine (59.62%) and combination was pheniramine + cetirizine (16.43%). H2 blockers were prescribed to 91 patients (42.7%), ranitidine being the one and only H2 blocker prescribed. Conclusion: Secondgeneration antihistamines were more commonly prescribed compared to first-generation drugs. Cetirizine was the most commonly prescribed antihistamine, and pheniramine + cetirizine was the most prescribed combination. A substantial number of patients were prescribed H2 blockers also which indicates the higher proportion of resistant dermatological conditions.

Rupatadine 20 mg and 40 mg are Effective in Reducing the Symptoms of Chronic Cold Urticaria.

Chronic cold urticaria (ColdU) is a rare disease characterized by mast cell-mediated wheals and angioedema following cold exposure. Second-generation H1-antihistamines, such as rupatadine, are the recommended first-line therapy. As of yet, the effects of rupatadine up-dosing on development of ColdU symptom have only been partially characterized. Two-centre, randomized, double-blind, 3-way crossover, placebo-controlled study in patients with a confirmed ColdU was designed to assess the effects of up-dosing of rupatadine. A total of 23 patients were randomized to receive placebo, rupatadine 20 mg/day, and rupatadine 40 mg/day for 1 week. The primary outcome was change in critical temperature thresholds and critical stimulation time thresholds after treatment. Secondary endpoints included assessment of safety and tolerability of rupatadine. Both 20 and 40 mg rupatadine were highly effective in reducing critical temperature thresholds (p < 0.001) and critical stimulation time thresholds (p < 0.001). In conclusion, rupatadine 20 and 40 mg significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects.

Allergy, Histamine and Antihistamines.

This chapter concentrates on the role in allergic disease of histamine acting on H1-receptors. It is clear that allergy has its roots in the primary parasite rejection response in which mast cell-derived histamine creates an immediate hostile environment and eosinophils are recruited for killing. This pattern is seen in allergic rhinitis where the early events of mucus production and nasal itching are primarily histamine mediated whereas nasal blockage is secondary to eosinophil infiltration and activation. In asthma, the role of histamine is less clear. Urticaria is characterized by mast cell driven pruritic wheal and flare-type skin reactions that usually persist for less than 24 h. Although the events leading to mast cell degranulation have been unclear for many years, it is now becoming evident that urticaria has an autoimmune basis. Finally, the properties of first- and second-generation H1-antihistamines and their role in allergic is discussed.

Successful Treatment of the Different Urticaria Subtypes

Whereas acute spontaneous urticaria is self-limiting and easy to treat, the management of chronic urticaria subtypes is often problematic. In principle, every urticaria should be treated until it is gone paralleled by a maximization of quality of life, vigilance, work, or school ability and a minimization of drug-related side effects. Complete remission can be achieved by treating or eradicating potential triggering factors, e.g., persistent infections. In daily practice, it is very useful to follow the current treatment algorithm that has been proposed by the international urticaria guidelines published in 2014. According to the first step of this algorithm, second-generation H1 antihistamines in standard dose are recommended. If this does not result in complete symptom control at step two, the dose is increased up to fourfold considering possible side effects. If this step is not sufficient, add-on treatment with either omalizumab, cyclosporine A, or montelukast is indicated. After the guideline consensus in many countries, omalizumab has received approval for the treatment of chronic spontaneous urticaria that is refractory to H1-antihistamines. The risk-benefit profile of each treatment approach should be carefully considered, and at least every 3–6 months, the need for ongoing treatment should be controlled.

Approaches to the diagnosis and management of chronic urticaria in children.

Most guidelines for chronic urticaria (CU) in infants and children are based on limited pediatric evidence. Current evidence used to guide treatment in children is extrapolated from data focusing on older age groups. CU in children is a different and complex condition than that in adults. Furthermore, there is little published information regarding urticaria in Korean children. The aim of the present article is to review recent research on chronic childhood urticaria and improve the current understanding of its pathogenesis and management. The classification and definition of urticaria in adults also applies to children. CU is defined as a daily occurrence of spontaneous wheals, angioedema, or both for >6 weeks. The precise pathophysiology of CU is unknown and the rates of successful identification of a cause in children with CU vary from 20%-50%. There is no established laboratory test to evaluate the presence of urticaria. The natural course of childhood CU is undetermined, with limited reports discussing long-term outcomes. Second-generation H1 antihistamines are the cornerstone of management, while limited therapeutic drugs are available for adults.

ASSURE-CSU: a real-world study of burden of disease in patients with symptomatic chronic spontaneous urticaria.

BackgroundChronic spontaneous urticaria (CSU) formerly known as chronic idiopathic urticaria (CIU) is a severe and distressing skin condition that remains uncontrolled in approximately one half of patients, despite the use of licensed, recommended doses of modern, second-generation H1-antihistamines. So far, the humanistic, societal and economic burden of CSU/CIU has not been well quantified. Therefore it is important to broaden our understanding of how CSU/CIU impacts patients, society, and healthcare systems, by determining the disease burden of CSU/CIU and the associated unmet need; as well as to further guide the use of new treatments in an efficient and cost-effective manner.MethodsASSURE-CSU is an observational, multicenter study being conducted in the UK, Germany, Canada, France, Italy, Spain, and The Netherlands. The study comprises a retrospective medical chart review in conjunction with patient surveys (including validated tools for assessment of disease impact) and an 8-day patient diary. The primary objectives of the study are to describe patient demographics, medical history, treatments, and healthcare resource utilization based on medical-record data and to assess the impact of disease, healthcare resource utilization, work days missed, and productivity loss based on patient-reported data. Approximately 700 patients (aged ≥18 years) will be enrolled who have CSU/CIU despite currently receiving treatment, and have had persistent symptoms for at least 12 months. Data will be collected retrospectively for the 12 months (±1 month) prior to enrolment wherever possible, and prospectively for the week following enrolment.DiscussionASSURE-CSU will be the first study to examine the economic and humanistic burden of disease in patients diagnosed with CSU/CIU who are symptomatic despite treatment. By combining retrospective evaluation of medical records with prospective patient surveys and 8-day diaries, across seven different countries, the ASSURE-CSU study will contribute to a better understanding and acknowledgement of the burden of disease in patients with symptomatic chronic spontaneous urticaria.

Update on Antihistamine Treatment for Chronic Urticaria in Children

Urticaria is a heterogeneous group of diseases, which may have different causes and mechanisms but share similar clinical features. It is clinically defined by the presence of wheals and/or angioedema. The diagnosis of urticaria is based on the evaluation of clinical manifestations. Urticaria is conventionally classified as acute or chronic. Chronic urticaria (CU) has been defined as daily or nearly daily occurrence of wheals and/or angioedema lasting longer than 6 weeks. Very little is known of the epidemiology of urticaria in infants and children, and still less is known of the prevalence of CU. The prevalence of CU in children is reported to vary between 0.1 and 0.3 %. The natural history of CU in children tends toward spontaneous resolution: approximately 25 % of patients go into remission within 3 years. Many etiological factors have been associated with CU, but most cases remain idiopathic despite exhaustive investigations. Among the non-idiopathic CU cases, the most common etiologies are autoimmune origin, followed by physical triggers. Food allergy and intolerance, as well as infections, are other less frequent possible causes. However, well-controlled studies to support the different etiologies and/or associations are lacking. The management of childhood CU includes identification and elimination of the triggering factors and symptomatic pharmacological treatment when symptoms appear. The first-line symptomatic therapy is second-generation H1-antihistamines, with dose adjustment for pediatric use. Only a few H1-antihistamines have been investigated for safety in children: cetirizine, levocetirizine, loratadine, fexofenadine, desloratadine, and rupatadine; of these, cetirizine and levocetirizine are the ones that have been most thoroughly investigated for long-term safety and efficacy in children ranging from 6 months to 12 years of age. Corticosteroids and other immunosuppressive drugs (e.g., cyclosporine A, dapsone, and omalizumab) should be restricted to very refractory CU cases and used only for a very short period.

A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis.

BackgroundThe capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible.MethodsWe performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo.ResultsTwenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast.ConclusionsIn an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.

Chronic urticaria in children

Although it is difficult to find a cause of chronic urticaria in children, previous studies have been identified some triggers, such as autoimmunity, physical stimuli, food and its additives, and infection. History taking and physical examination remain the best tool for identifying an underlying cause of urticaria. First investigations include a complete blood count with differential, erythrocyte sedimentation rate, and C-reactive protein in children with chronic urticaria. If physical stimuli are suspected as triggers of chronic urticaria, appropriate provocation tests can be performed. Although the frequency of autoimmune urticaria was relatively high compared to the other causes in children with chronic urticaria, it is not easy to apply routine use of autologous serum skin tests to clinical practice. Additional extensive laboratory investigations are not required in the majority of cases. Second-generation H1-antihistamines are the mainstay of treatment from current guidelines in children with chronic urticaria, and dosage can be increased if the standard dose is not effective. Data on chronic urticaria in children are scarce, and causes have been considered to be similar to those in adults. Therefore, diagnostic approaches and treatment principles of chronic urticaria in children have been derived from extrapolating data in adults. In the future, comparative studies for the causes of chronic urticaria between children and adults, and therapeutic modalities for refractory cases will be needed. (Allergy Asthma Respir Dis 2014;2:236-242)

Phenolic Compounds from the Flower of Stewartia pseudo-camellia and Their Inhibitory Effects on the Release of β-Hexosaminidase in RBL-2H3 Cells

Stewartia pseudo-camellia Maxim. (=S. koreana Nakai) is a deciduous tree in the family Theaceae which is distributed in southern Korea [1]. Its fruit or bark of stem and root have been used as a folk medicine for the treatment of circulatory disorders, paralysis of the limbs, legs and arms, and several pains. Previous studies on S. pseudo-camellia, have investigated several biological activities including angiogenesis [2], anti-inflammation [3, 4], prevention and treatment of osteoporosis [5], and anti-oxidative effect [6]. The flower of S. pseudo-camellia was consecutively extracted with hexane and MeOH. The anti-allergic activity of MeOH extract was comparatively higher than that of second-generation H1-antihistamine ketotifen as positive control. A new compound together with nine known compounds, (+)-catechin, quercetin-3-rhamnoside, methyl gallate, (-)-epicatechin, afzelin, aromadendrin, myricetin, kaempferol-7-O-rhamnosyl-3-O-rutinoside, and kaempferol-7-O-(4-O-acetylrhamnosyl)-3-O-rutinoside were isolated from the MeOH extract. The structure of a new phenolic compound, named pseudocamellianin A, was determined as kaempferol-7-O-(4-O-acetylrhamnosyl)-3-O-(4'-O-p-coumaroyl)rutinoside from its spectral data. The anti-allergic activity of isolated compounds was evaluated in an in vitro assay on β-hexosaminidase release inhibition using RBL-2H3 cells stimulated by DNP-BSA. Among tested compounds, quercetin-3-rhamnoside, afzelin, aromadendrin, myricetin exhibited similar activity with ketotifen.

Evaluation of the Single-dose Pharmacokinetics of Bilastine in Subjects with Various Degrees of Renal Insufficiency

BackgroundBilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries.ObjectiveThis study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin.MethodsThe study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18–80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m2]; (2) mild renal insufficiency (GFR 50–80 mL/min/1.73 m2); (3) moderate renal insufficiency (GFR 30–50 mL/min/1.73 m2); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m2). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics.ResultsThere was a clear trend of increasing area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) through the groups 1–4. The mean AUC from time zero to infinity (AUC∞) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC∞ and AUC from time zero to time of last measurable plasma concentration (AUClast) were not within the 0.8–1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h.ConclusionAn oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CLP/F)/CLR] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Terpenes and Phenolic Compounds from Agastache rugosa and Their Inhibitory Effect on the Release of β-Hexosaminidase in RBL-2H3 Cells

Agastache rugosa (Fisch. et Meyer) O. Kuntze., commonly known as Korean mint, is a perennial herb in the family Labiatae which is distributed in Korea, China, Japan and Russia. The herb has been used for the treatment of summer flu, summer cold, headache, stomachache, nausea, vomiting, and dyspepsia in Chinese and Korean traditional medicines. Previous studies on A. rugosa, have investigated several biological activities including antioxidative, antibacterial, antiviral, antifungal, and anticancer activities. In continuation of our search for anti-allergic compound from natural products, we have found that the hexane extract of A. rugosa has anti-allergic activity. The dried aerial part of A. rugosa was extracted with hexane. The anti-allergic activity of the hexane extract was comparatively higher than that of second-generation H1-antihistamine ketotifen as positive control. Twelve terpenes and phenolic compounds were isolated from the hexane extract. The structures of isolated compounds were identified as linalool, trans-isopulegone, linalyl acetate, β-caryophyllene, eugenol, estragole, cis-jasmone, phytol, l-menthone, methyl eugenol, and trans-carveol by comparison of their spectral data with literature values. The anti-allergic activity of isolated compounds was evaluated in an in vitro assay on β-hexosaminidase release inhibition using RBL-2H3 cells stimulated by DNP-BSA.

Allergic diseases of the skin and drug allergies – 2022. Consensus statement on management of urticaria in India

Background Urticaria, a heterogeneous group of diseases, often cannot be recognized by its morphology. Due to non-specific and non-affordable diagnosis, management of urticaria, especially chronic urticaria, is very challenging. This guideline includes definition, causes, classification and management of urticaria. Urticaria has a profound impact on the quality of life and causes immense distress to patients, necessitating effective treatment. One approach to manage urticaria is identification and elimination of the underlying cause(s) and/or eliciting trigger (s), while the second one is treatment aimed at providing symptomatic relief. This guideline recommends use of second-generation non-sedating H1 antihistamines as the first-line treatment. The dose can be increased up to four times to meet the expected results. In case patients still do not respond, appropriate treatment options can be selected depending on the cost. First-generation antihistamines can interfere with rapid eye movement (REM) sleep and impact on learning and performance. New GA²LEN/EDF/EAACI/WAO guidelines do not recommend the use of these sedating antihistamines for the routine management of CU as the firstline agents. Second-generation antihistamines should be considered as the first-line symptomatic treatment for urticaria because of their good safety and tolerability pro