piperidines and Urticaria

Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent.. We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria.. We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software.. We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo.. Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.

Topics: Benzimidazoles; Chronic Urticaria; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Urticaria

Topics: Adolescent; Adult; Benzimidazoles; Child; Drug Interactions; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Quality of Life; Rhinitis, Allergic; Urticaria; Young Adult

Introduction: Allergic conditions frequently require treatment with antihistamines. First-generation antihistamines can potentially interfere with restful sleep, cause “morning after” effects, impair learning and memory, and reduce work efficiency. Second-generation antihistamines, such as bilastine, have been demonstrated to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events.\ \ Method: A real-world case project was developed to help optimize patient care by recognizing the role bilastine can play for allergic conditions where antihistamine treatment is needed. The presented real-world patient cases conducted by the panel members are supported with evidence from the literature, where available. Any discussion concerning off-label use should be considered an expert opinion only.\ \ Results: The real-world cases presented here used bilastine in conditions such as perennial and seasonal allergic rhinitis, chronic urticaria, as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions. The treated patients were between 9 and 76-years old providing information on a full spectrum of patients that require treatment with antihistamines.\ \ Conclusions: The presented real-world cases using the second-generation antihistamine, bilastine, demonstrated favorable outcomes for the treated patients. While effectively relieving symptoms, the antihistamine was reported to be safe and well-tolerated.\ \ J Drugs Dermatol. 2020;19(2)145-154. doi:10.36849/JDD.2020.4835

Topics: Adolescent; Adult; Aged; Benzimidazoles; Child; Histamine Antagonists; Humans; Hypersensitivity; Middle Aged; Piperidines; Urticaria; Young Adult

Histamine, acting predominantly via the H1-receptor, is an important mediator of the symptoms of allergy. H1-antihistamines, which stabilize the receptor in its inactive form, are the treatment of choice for some chronic allergic conditions. Ebastine is a well-established secondgeneration oral H1-antihistamine that is administered once daily at a dose of 10-20 mg and is available both as a standard tablet and as a fast-dissolving tablet that disintegrates in the mouth. Ebastine has been shown to relieve symptoms in patients with allergic rhinitis or urticaria in multiple clinical trials. In addition to its antihistamine effects, the drug has modulating effects on the allergic inflammatory process, thus potentially explaining its beneficial effect on nasal obstruction in some patients. Ebastine is generally well tolerated at recommended doses and is one of the lowest-risk antihistamines with respect to adverse cognitive/psychomotor effects, as confirmed by decades of pharmacovigilance. New long-term data confirm its efficacy and tolerability during up to 1 year of treatment in patients with chronic urticaria.

Topics: Administration, Oral; Butyrophenones; Histamine; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic; Treatment Outcome; Urticaria

Urticaria is a highly prevalent disease among people. First-choice treatment continues to be centred on the second-generation H1 antihistamines, including a wide group of drugs with a better therapeutic index (or risk:benefit ratio) than the classic ones, even in the high, off-label dosage occasionally required in chronic urticaria. Bilastine is a newly registered H1-antihistamine for treatment of allergic rhinoconjunctivitis and urticaria. With established antihistaminic and antiallergic properties, it is widely reviewed in the medical literature; however, to our knowledge, a specific review of bilastine's role in the treatment of urticaria was lacking.. This article reviews the medical literature on the effectiveness and safety of bilastine in urticarial syndromes, either spontaneous or inducible, by means of a Medline search from 1990 to present, completed with some nonpublished data provided by the manufacturer.. Once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life in chronic urticaria, with at least comparable efficacy to levocetirizine. As far as studies in healthy volunteers, clinical assays, and recent clinical experience can establish, bilastine's safety profile is adequate, appearing to be entirely free from cardiovascular effects, and not impairing psychomotor performance or actual driving, even at twice the therapeutic dose.

Topics: Animals; Benzimidazoles; Histamine Antagonists; Humans; Piperidines; Treatment Outcome; Urticaria

Bepotastine besilate 1.5% is a newly approved second-generation topical antihistamine indicated for the pruritus associated with allergic conjunctivitis. In Japan, the oral formulation is approved to manage pruritus associated with allergic rhinitis and urticaria.. Bepotastine is a piperidine derivative that antagonizes H1 receptors with high selectivity. It has been labeled a dual-acting or multiple-acting antiallergic medication, because it inhibits histamine at H1 receptors and stabilizes mast cells to prevent histamine release. Bepotastine may also have other immunoactive properties, such as inhibition of eosinophil migration, interleukin-5 (IL-5), leukotrienes (e.g., LTB4) and platelet-activating factor (PAF). Human clinical trials demonstrate the efficacy and safety of systemic and ophthalmic bepotastine for pruritus relief, limited penetration across the blood-brain-barrier and kinetics suitable for twice-daily administration.. Bepotastine besilate 1.5% ophthalmic solution is a safe and effective treatment option for allergic conjunctivitis associated pruritus. Side-effect profile is similar to other ocular antihistamine agents. Additional comparative-effectiveness studies would further advance its clinical use. Oral bepotastine is a safe and effective treatment option approved in Japan for allergic rhinitis, urticaria and pruritus associated with skin diseases.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

The year 2012 has seen relevant changes in Polish pharmaceutical legislation and drug reimbursement, among others limiting the reimbursement solely to indications stated in the Summaries of Product Characteristics (SPCs). A discrepancy with expert recommendations became apparent. The aim of this study was to analyze discordances between up-to-date expert recommendations, the SPCs in force, and the evidence for the effectiveness of recommended drugs in urticaria. Guidelines for the treatment of urticaria issued by Polish and international expert bodies were analyzed, along with the SPCs. A systematic review of clinical trials of recommended drugs was carried out. Of drugs recommended by the experts, 203 were authorized in Poland for urticaria treatment, including 167 oral preparations of second-generation antihistamines (SGAH, 8 active substances), 29 oral preparations of first-generation antihistamines (6 substances), 4 preparations of systemic glucocorticosteroids (2), 2 topical glucocorticosteroid preparations (2) and one combined preparation of human immunoglobulin with histamine. Among products both recommended by experts and licensed for the treatment of urticaria in Poland, high or moderate-level of evidence of effectiveness was available for 7 active substances (bilastine, cetirizine, desloratadine, fexofenadine, loratadine, levocetirizine, rupatadine). Nevertheless, 39% of SGAH available in Poland (66 preparations of cetirizine, emedastine, levocetirizine, loratadine or fexofenadine) were registered exclusively for "chronic idiopathic urticaria" - a diagnosis inconsistent with the current state of medical knowledge. We conclude that there exist considerable discrepancies between expert recommendations for the pharmacotherapy of urticaria, the licensed use of drugs as defined in Summaries of Product Characteristics and scientific evidence for their effectiveness.

Topics: Administration, Oral; Administration, Topical; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Glucocorticoids; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Poland; Practice Guidelines as Topic; Terfenadine; Treatment Outcome; Urticaria

Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

Topics: Automobile Driving; Benzimidazoles; Cardiovascular Diseases; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Urticaria

Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.

Topics: Area Under Curve; Benzimidazoles; Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Urticaria

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Topics: Animals; Automobile Driving; Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria; Wakefulness

New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements.. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria.. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

Topics: Animals; Benzimidazoles; Clinical Trials, Phase I as Topic; Histamine H1 Antagonists; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Urticaria

The evaluation of quality of life (QoL) and its modification through therapeutic interventions has become a prioritary concern in recent years and a requirement on the part of regulatory agencies for the authorization of new drugs. In clinical studies of allergic disorders, particularly allergic rhinitis and urticaria, different types of generic questionnaires have been used - especially disease specific instruments such as the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) or skin disease specific tools such as the Dermatology Life Quality Index (DLQI). Throughout its clinical development, bilastine has been shown to be more effective than placebo and at least as effective as cetirizine, levocetirizine, fexofenadine or desloratadine in controlling the symptoms of seasonal allergic rhinitis and chronic urticaria. QoL has been studied as a secondary objective in three allergic rhinitis clinical trials, using the RQLQ, in a total of 2335 patients. Likewise, in chronic urticaria, QoL has been evaluated using the DLQI in a total of 525 patients, versus levocetirizine and placebo. The improvement in the QoL parameters in these studies (RQLQ or DLQI domains) at all times proved proportional to the symptoms improvement. In general, the data obtained relating to changes in QoL are concordant with the mean global visual analog scale (VAS in mm) values and their changes, from the beginning until the end of the treatment period, for all of the trials, for bilastine and all its comparators.

Topics: Benzimidazoles; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Oral bepotastine is a second-generation histamine H(1) receptor antagonist that also suppresses some allergic inflammatory processes. Numerous short- and long-term clinical trials and surveillance studies have shown that twice-daily bepotastine is an effective and generally well tolerated antihistamine in the treatment of patients with allergic rhinitis, chronic urticaria or pruritus associated with skin conditions (eczema/dermatitis, prurigo or pruritus cutaneus). Bepotastine 20 mg/day was significantly more effective than terfenadine 120 mg/day in patients with perennial allergic rhinitis, as evaluated by the final global improvement rating and several other endpoints in a phase III trial. In phase III trials in patients with chronic urticaria, bepotastine 20 mg/day was more effective than placebo in improving levels of itching and eruption, and as effective as terfenadine 120 mg/day with regard to the final global improvement rating and other endpoints. In a noncomparative trial in patients with pruritus associated with skin diseases, the majority of bepotastine recipients in the overall population, as well as in the specific skin disease subgroups (eczema/dermatitis, prurigo or pruritus cutaneus), had a final global improvement rating of moderate or greater. Bepotastine was generally well tolerated in adult and paediatric patients with allergic conditions.

Topics: Administration, Oral; Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Hypersensitivity; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic, Perennial; Urticaria

Histamine is a key mediator in the development of allergy symptoms, and oral H(1)-antihistamines are among the most widely used treatments for symptomatic relief in conditions such as allergic rhinitis and chronic urticaria. Ebastine is a second-generation antihistamine which has been shown to be an effective treatment for both seasonal and perennial allergic rhinitis. In controlled clinical trials in adult and adolescent patients with allergic rhinitis, ebastine 10 mg once-daily improved symptoms to a significantly greater extent than placebo and to a similar extent as loratadine 10 mg and cetirizine 10 mg (both once-daily), while ebastine 20 mg proved to be more effective than these two comparator antihistamines. In addition, ebastine was significantly more effective than placebo at relieving the symptoms of chronic idiopathic urticaria. Ebastine provides efficacy throughout the 24-h dosing interval with once-daily administration and clinical benefit is seen from the first day of treatment. Small studies have found beneficial effects for ebastine in patients with other disorders, including cold urticaria, dermographic urticaria, atopic asthma, mosquito bites and (in combination with pseudoephedrine) the common cold. In addition to the regular ebastine tablet, a fast-dissolving tablet (FDT) formulation, which disintegrates in the mouth without the aid of a drink, is also available. It has been shown to be bioequivalent to the regular tablet, and to be significantly more effective than desloratadine at reducing histamine-induced cutaneous wheals. A number of patient surveys demonstrated that the majority of individuals who tried the fast-dissolving formulation reported it to be convenient for use, fast-acting and preferred it to their previous antihistamine medication. Perhaps most importantly, a large proportion of patients indicated that they would prefer to use this new formulation in the future. Ebastine has a rapid onset of action and it can be administered once-daily, with or without food. Dose modifications are not needed in elderly patients, or in those with renal or mild to moderate hepatic impairment. Ebastine is generally well-tolerated, and clinical studies showed that at usual therapeutic doses of 10 and 20 mg once-daily, it had no clinically relevant adverse effects on cognitive function and psychomotor performance or on cardiovascular function. In conclusion, ebastine is an effective and generally well-tolerated treatment for allergic rhini

Topics: Animals; Butyrophenones; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.

Topics: Anti-Allergic Agents; Asthma; Butyrophenones; Clinical Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Topics: Adolescent; Benzimidazoles; Child; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Treatment Outcome; Urticaria

The aim of this study was to compare the pharmacodynamic activity of bilastine administered under fasting and fed conditions in healthy volunteers.. In this randomized, open-label, two-period, crossover study involving 24 healthy subjects, once-daily oral bilastine 20 mg was administered for 4 days under fasting and fed conditions, with a 7-day washout period. Bilastine plasma concentrations were measured for 24 h after the first and fourth doses in each period. Pharmacodynamic activity was assessed by wheal and flare surface inhibition and subjective assessment of itching, after intradermal injection of histamine 5 μg.. When administered under fed versus fasting conditions, exposure to bilastine 20 mg decreased (mean maximum plasma concentration and area under the curve from time 0 to 24 h decreased by 34.27% and 32.72% [day 1], respectively, and 33.08% and 28.87% [day 4]). Despite this, the antihistaminic effect of bilastine 20 mg was not altered by food. On day 1, as assessed by wheal and flare surface inhibition, the maximum effect and duration of action of bilastine did not differ to a significant extent between fasting and fed conditions, with only a short 30-min delay in the onset of wheal inhibition. At steady state (day 4), bilastine's pharmacodynamic effects were not significantly affected under fasting or fed conditions.. The pharmacokinetic interaction of bilastine with food does not imply a significant reduction of its peripheral antihistaminic efficacy. Despite a slight delay in onset of action on the first treatment day, the global clinical efficacy of bilastine is not affected by coadministration with food.

Topics: Area Under Curve; Cross-Over Studies; Food-Drug Interactions; Humans; Piperidines; Urticaria

Chronic spontaneous urticaria (CSU) is a debilitating condition, adversely affecting the patient's quality of life. Bilastine is a recently introduced, non-sedative H1-antihistamine for its treatment. We wanted to compare the effectiveness, safety, and tolerability of bilastine 20 mg vs levocetirizine 5 mg in moderate-to-severe CSU. We conducted a double-blind, randomized controlled trial with two groups: bilastine 20 mg (n = 31) and levocetirizine 5 mg (n = 27), once daily for 42 days. We included patients (18-65 years), with moderate-to-severe CSU. UAS7, VAS, and DLQI were used to assess severity of urticaria, global urticaria-induced discomfort and quality of life, respectively. DLQI was assessed at baseline (D0) and end-of-treatment (D42), while UAS7 and VAS were noted at baseline and all follow-up visits. Assessment of UAS7 alteration was our primary objective, while changes in DLQI and VAS were the secondary outcomes. Safety was assessed by recording drug-related adverse events, biochemical investigations, and electrocardiogram, along with tolerability and compliance. Both drugs significantly improved UAS7, DLQI, and VAS at end-of-treatment (D42) compared with baseline (intra-group). At the end-of-treatment, all parameters showed greater improvement with bilastine, but only UAS7 reduction was significant (bilastine > levocetirizine, P = .03). In both the groups, UAS7 and VAS improved significantly D14 onwards, and was maintained throughout the study. Sedation was significantly less with bilastine (P = .04), while neither drug showed any serious adverse-effect. Tolerability of both drugs was similar. Therefore, bilastine was found to be a more effective and less-sedative novel therapy for CSU compared to levocetirizine, with similar effect on quality of life.

Topics: Benzimidazoles; Cetirizine; Chronic Disease; Chronic Urticaria; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Quality of Life; Treatment Outcome; Urticaria

Bilastine is a highly selective, non-sedating antihistamine, indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Available data suggest that bilastine interferes neither with driving ability nor with flying-related performance. However, no data are available on the effect of bilastine on the driving ability in extreme conditions. Here we analyzed the effect of 7 days treatment with 20 mg bilastine in patients with allergic rhinitis and/or chronic urticaria, on psychophysical performance assessed by the Formula One (F1) high-speed simulator-driving test.. This study is a phase IV, interventional, prospective, mono-centric, single arm, open-label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic urticaria, able to perform a preliminary driving test on F1 simulator were considered (V-1). First, the patients had a screening visit to assess their eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment and Visit 2 (V2), at the end of bilastine treatment. The primary variable parameter was the ability to maintain the vehicle in a central position at different speeds (50, 150, and 250 km/h).. Bilastine had a good safety profile and was well tolerated in terms of adverse events, laboratory parameters and vital signs. Bilastine did not have any negative effect on the ability to maintain the requested path, a constant speed as well as on attention and reactivity levels, even in extreme driving conditions.. This study is the first done in patients with allergic rhinitis and/or chronic urticaria using a F1-high speed simulator-driving test evaluating subjects' performance under bilastine treatment.

Topics: Adult; Attention; Automobile Driving; Benzimidazoles; Chronic Disease; Computer Simulation; Dizziness; Female; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Rhinitis, Allergic; Urticaria; Young Adult

Bilastine, a novel non-sedating second-generation H. We 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.. A 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.. Two-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.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Chronic Disease; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Phenotype; Piperidines; Quality of Life; Treatment Outcome; Urticaria; Young Adult

A number of second-generation non-sedating antihistamines are used in clinical practices over the world. However, long-term safety and efficacy have not been proved high level evidence based medicine. We have performed an open-label, multicenter, phase III study to evaluate the long-term safety and efficacy of bilastine, a novel non-sedating H

Topics: Adult; Benzimidazoles; Chronic Disease; Eczema; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Long Term Adverse Effects; Male; Middle Aged; Piperidines; Prurigo; Pruritus; Quality of Life; Severity of Illness Index; Treatment Outcome; Urticaria

Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.. In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18-75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8-24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073.. Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible responses [weighted generalised estimating equation]) compared with 7·4% for placebo (48·9 of 656·5; difference 11·3%; odds ratio 3·6; 95% CI 1·2-10·8; p=0·0076). Frequent severe adverse events (>4% difference from placebo) were diarrhoea (eight [11%] of 70 in the masitinib group vs one [2%] of 63 in the placebo group), rash (four [6%] vs none), and asthenia (four [6%] vs one [2%]). The most frequent serious adverse events were diarrhoea (three patients [4%] vs one [2%]) and urticaria (two [3%] vs none), and no life-threatening toxicities occurred. One patient in the placebo group died (unrelated to study treatment).. These study findings indicate that masitinib is an effective and well tolerated agent for the treatment of severely symptomatic indolent or smouldering systemic mastocytosis.. AB Science (Paris, France).

Topics: Adult; Aged; Aged, 80 and over; Asthenia; Benzamides; Diarrhea; Double-Blind Method; Exanthema; Female; Humans; Male; Mastocytosis, Systemic; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyridines; Severity of Illness Index; Thiazoles; Treatment Outcome; Urticaria; Young Adult

Topics: Acetamides; Adolescent; Adult; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Male; Non-Neuronal Cholinergic System; Piperidines; Pyridines; Quality of Life; Urticaria; Young Adult

Regulations on medicinal products for paediatric use require that pharmacokinetics and safety be characterized specifically in the paediatric population. A previous study established that a 10-mg dose of bilastine in children aged 2 to <12 years provided an equivalent systemic exposure as 20 mg in adults. The current study assessed the safety and tolerability of bilastine 10 mg in children with allergic rhinoconjunctivitis and chronic urticaria.. In this phase III, multicentre, double-blind study, children were randomized to once-daily treatment with bilastine 10-mg oral dispersible table (n = 260) or placebo (n = 249) for 12 weeks. Safety evaluations included treatment-emergent adverse events (TEAEs), laboratory tests, cardiac safety (ECG recordings) and somnolence/sedation using the Pediatric Sleep Questionnaire (PSQ).. The primary hypothesis of non-inferiority between bilastine 10 mg and placebo was demonstrated on the basis of a near-equivalent proportion of children in each treatment arm without TEAEs during 12 weeks' treatment (31.5 vs. 32.5%). No clinically relevant differences between bilastine 10 mg and placebo were observed from baseline to study end for TEAEs or related TEAEs, ECG parameters and PSQ scores. The majority of TEAEs were mild or moderate in intensity. TEAEs led to discontinuation of two patients treated with bilastine 10 mg and one patient treated with placebo.. Bilastine 10 mg had a safety and tolerability profile similar to that of placebo in children aged 2 to <12 years with allergic rhinoconjunctivitis or chronic urticaria.

Topics: Adolescent; Adult; Benzimidazoles; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome; Urticaria

Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.. Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine.. Bilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly (P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treatment was well tolerated without evidence of increased sedation with dose escalation.. Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines.

Topics: Administration, Oral; Adult; Aged; Benzimidazoles; Chi-Square Distribution; Cold Temperature; Confidence Intervals; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Risk Assessment; Statistics, Nonparametric; Treatment Outcome; Urticaria; Young Adult

Comparison of bilastine and cetirizine in inhibiting skin wheal and flare responses over 24 h.. Twenty-one healthy male volunteers (aged 19-44 years).. Volunteers were randomised to receive single oral doses of 20 or 50 mg bilastine, 10 mg cetirizine 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.. There were no significant differences between overall inhibitions of wheal or flare by 20 mg bilastine and 10 mg cetirizine. Bilastine was faster in onset than cetirizine, inhibitions 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 (Student's t test). 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, Fisher's exact test). There were no significant differences between the drugs at later times. Bilastine 50 mg had a longer duration of action than bilastine 20 mg.. Both 20 mg bilastine and 10 mg cetirizine are effective and of long duration in reducing histamine-induced wheal and flare responses, the major difference between the two drugs being the more rapid onset of action of bilastine.

Topics: Adult; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Cross-Over Studies; Double-Blind Method; Histamine; Histamine H1 Antagonists; Humans; Male; Piperidines; Skin Tests; Urticaria; Young Adult

Bilastine is a novel nonsedative H(1)-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The aim of this study was to compare the clinical efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe symptoms.. Overall 525 male and female subjects aged 18-70 years were randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily for 28 days, in double-blind manner, in 46 centres across Europe and Argentina. Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for assessment of change from baseline in the total symptoms scores (TSS) over 28 days as the primary efficacy measure. Changes in reflective and instantaneous symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated discomfort and sleep disturbance were assessed as secondary outcomes. Safety was assessed according to adverse events, laboratory tests and electrocardiograms.. Bilastine reduced patients' mean reflective and instantaneous TSS from baseline to a significantly greater degree than placebo (P < 0.001); from day 2 onwards of treatment. The DLQI, general discomfort, and sleep disruption were also improved significantly in bilastine-treated patients as compared with placebo-treated patients (P < 0.001 for all parameters). Comparison with levocetirizine indicated both treatments to be equally efficacious as well as equally safe and well tolerated as compared with placebo.. Bilastine 20 mg is a novel effective and safe treatment option for the management of CU.

Topics: Adolescent; Adult; Aged; Area Under Curve; Benzimidazoles; Cetirizine; Chronic Disease; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Quality of Life; Urticaria; Young Adult

In dermographic urticaria (DU), shearing forces on the skin result in weals and itching. Second-generation antihistamines are recommended as the first-line treatment, but to date only a few have ever been tested for this condition. The objective of this pilot study was to assess the safety and efficacy of ebastine in preventing symptoms of DU. Seven adult patients with DU participated in a double-blind cross-over trial of ebastine 20 mg. Safety was assessed using a sensitive psychometric battery, testing cognitive performance and mood. Efficacy was assessed by rating weals, erythema, pruritus and burning after challenge. Ebastine had no negative effective on cognitive performance or mood. Weals, pruritus and burning were greatly reduced for most subjects. This pilot study suggests that ebastine is safe and effective in preventing the symptoms of DU and should be tested on a larger scale.

Topics: Adult; Affect; Aged; Butyrophenones; Cognition; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Physical Stimulation; Pilot Projects; Piperidines; Psychometrics; Treatment Outcome; Urticaria

Acquired cold urticaria (ACU) is a skin condition, in which exposure to cold results in wheals and itching and sometimes general systemic complications. It has a profound impact on patient quality of life. Second-generation antihistamines are recommended as the first-line treatment, but to date only a few have been scientifically tested for this condition.. To assess the safety and efficacy of ebastine in preventing ACU symptoms.. Twenty-two adult ACU patients participated in a double-blind crossover trial of 20 mg ebastine. The safety of ebastine was sensitively assessed with a psychometric battery testing cognitive performance and mood. After cold challenge, wheal and erythema were assessed by the investigator and the intensities of pruritus and burning were rated by the subject.. Ebastine had no negative impact on any of the parameters of cognitive performance or mood. It dramatically reduced the number of patients who experienced wheals, pruritus, and burning after challenge.. Ebastine is safe and effective in preventing the symptoms of ACU.

Topics: Adult; Affect; Butyrophenones; Cold Temperature; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Psychometrics; Treatment Outcome; Urticaria

Levocetirizine is the active enantiomer of cetirizine, a potent drug with little metabolism widely used for allergic rhinitis and urticaria.. This study compares the potency, consistency, onset, and duration of action of levocetirizine with other popular antihistamines.. Levocetirizine 5 mg, ebastine 10 mg, fexofenadine 180 mg, loratadine 10 mg, mizolastine 10 mg, or placebo in single doses were given to 18 healthy male volunteers in a double-blind, crossover, randomized fashion. Wheal-and-flare responses to epicutaneous histamine dihydrochloride (100 mg/mL) challenge were measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after each dose.. The overall effect of each drug was evaluated by the area under the curve (0 to 24 hours). Levocetirizine was the most potent and consistently effective drug for inhibiting the histamine-induced wheal-and-flare surface areas. Ebastine, fexofenadine, and mizolastine ranked next and had almost identical effects for inhibiting the wheal. Loratadine was the least potent drug. Levocetirizine, fexofenadine, and mizolastine inhibited the wheal-and-flare response after 1 hour and reached their peak for inhibition after 4 hours. Ebastine and loratadine could be distinguished from placebo only after 4 hours. After treatment with levocetirizine, all 18 subjects had >95% inhibition of the wheal response at one timepoint. Fexofenadine, mizolastine, and ebastine were inhibitory in declining order. All treatments were considered safe and well tolerated.. Levocetirizine, the active enantiomer of cetirizine, is more potent and consistent than other popular H1 antihistamines for blocking the cutaneous response to histamine. These findings may predict the efficacy of this drug in treating allergic disorders.

Topics: Adult; Benzimidazoles; Butyrophenones; Cetirizine; Cross-Over Studies; Double-Blind Method; Histamine; Histamine H1 Antagonists; Humans; Loratadine; Male; Piperidines; Terfenadine; Treatment Outcome; Urticaria

New H1-antagonists have become available, but there has been no comparison of their potency for inhibiting histamine in the skin.. Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 60 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healthy male volunteers in a double-blind, crossover randomized manner. Inhibition of the wheal and flare response to epicutaneous histamine phosphate (100 mg/ml) challenge was measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after doses.. Epinastine inhibited the wheal and flare after 30 min. Cetirizine commenced acting at 1 h and was superior to other treatments. Ebastine was no better than placebo until 4 h, but was efficacious thereafter until 24 h. Terfenadine induced potent inhibition after 1 h and was superior to its metabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibition of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0-24 h) was cetirizine, epinastine, terfenadine, ebastine, fexofenadine, loratadine, and placebo.. The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.

Topics: Adult; Butyrophenones; Cetirizine; Cross-Over Studies; Dibenzazepines; Double-Blind Method; Histamine; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity, Immediate; Imidazoles; Loratadine; Male; Piperidines; Skin Tests; Terfenadine; Urticaria

Ebastine is a new second generation histamine H1 receptor antagonist that has shown clinical efficacy in the treatment of seasonal and perennial allergic rhinitis and chronic urticaria after once-daily administration. This double-blind multicentre randomised placebo-controlled study has investigated the long term efficacy of ebastine 10mg once daily in the treatment of chronic urticaria compared with that of terfenadine 60mg twice daily. At the end of a 3-month treatment period, ebastine was significantly superior to placebo in improving symptoms of chronic urticaria (including severity of itching, number of wheals per day), and its efficacy was similar to that of terfenadine. In a global assessment of efficacy, investigators considered chronic urticaria to have improved in 73% of ebastine recipients compared with 68% and 52% of patients treated with terfenadine or placebo, respectively. The patients' assessments of efficacy were similar to those of the investigators. Ebastine was well tolerated, the incidence and nature of adverse events with this agent being similar to those reported in patients treated with terfenadine or placebo. The most common adverse events were headache and dry mouth. Thus, these results, which show ebastine to be an effective and well tolerated agent, indicated that the drug should be considered for the first-line therapy of chronic urticaria.

Topics: Adult; Anti-Allergic Agents; Butyrophenones; Chronic Disease; Double-Blind Method; Histamine H1 Antagonists; Humans; Piperidines; Terfenadine; Urticaria

The new antihistamine, HC20-511 (Sandoz), was compared with Dimetinden (Fenistil retard) in a single-blind comparative study in 42 patients with dermatoses, 28 of whom suffered from chronic urticaria. HC20-511 had a better effect, especially in chronic urticaria, where pruritus, erythema and papules quickly disappeared. The effect appeared somewhat faster than and lasted as long as that of Dimetinden, although HC20-511 is not a retard-preparation unlike the Dimetinden preparation used for comparison. HC20-511 also caused less side effects.

Topics: Adolescent; Adult; Aged; Chronic Disease; Clinical Trials as Topic; Dimethindene; Drug Therapy, Combination; Female; Fumarates; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Pruritus; Skin Diseases; Thiophenes; Urticaria; Vomiting

Topics: Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Delayed-Action Preparations; Dermatitis; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Placebos; Pruritus; Tablets; Time Factors; Urticaria

We report a case of late-onset Schnitzler syndrome successfully treated with Janus-activated kinase (JAK) inhibitors and colchicine. Schnitzler syndrome should be considered for recurrent chronic urticaria when accompanied by fever, fatigue, rapid weight loss, and poor response to antihistamine treatment. Skin biopsy, bone marrow biopsy, and electrophoresis help confirm the diagnosis. Early diagnosis and treatment can lead to complete resolution of symptoms. Besides interleukin (IL)-1 and IL-6 inhibitors, JAK inhibitors and colchicine may be considered as other choices of treatment.

Topics: Colchicine; Humans; Interleukin-1; Piperidines; Schnitzler Syndrome; Urticaria

Topics: Acrylic Resins; Administration, Cutaneous; Animals; Butyrophenones; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Carriers; Drug Liberation; Drug Stability; Emulsions; Gels; Histamine H1 Antagonists; Hydrogen-Ion Concentration; Male; Piperidines; Rabbits; Rheology; Urticaria; Viscosity

The second-generation antihistamines at licensed doses are first-line treatment in urticaria and up-dosing is recommended as second-line treatment. To assess the efficacy and safety of escalated doses of ebastine in patients with chronic urticaria (CU), we designed this study. Recruited patients with CU were treated with increasing doses of ebstine. Treatment started at the daily dose of 10 mg. The symptom is assessed weekly, and if there is no significant improvement, the dose is increased from 10 mg to 20 mg, and if still no significant improvement, up to 40 mg. Pruritus, number, diameter, duration and frequency of wheals, and adverse reactions were assessed. One hundred and forty (76.50%) patients achieved marked effect with ebastine 10 mg/day, 27 (14.75%) patients with ebastine 20 mg/day and 13 (7.10%) patients with ebastine 40 mg/day, while 3(1.64%) patients did not get marked effect. There was no significant difference of effect between factitious urticaria, CSU, cholinergic urticaria and CSU with factitious urticaria in different dose (all p > 0.05). Common adverse reactions of ebstine treatment, included dry mouth, somnolence, tiredness and headache, were mild or moderate. There was no significant difference between the degree score of dry mouth with different doses of ebastine, and the same to somnolence, tiredness and headache (all p > 0.05). Doses escalation of ebastine should be effective in treatment of factitious urticaria, CSU and cholinergic urticaria with poorly treated by standard of double doses. Increasing ebastine dose did not increase the incidence of adverse reactions.

Topics: Butyrophenones; Cholinergic Agents; Chronic Disease; Chronic Urticaria; Headache; Histamine H1 Antagonists; Humans; Piperidines; Prospective Studies; Sleepiness; Urticaria; Xerostomia

Schnitzler syndrome is a rare adult-onset acquired autoinflammatory disorder typically characterized by chronic urticarial rash and immunoglobulin M (IgM) (rarely IgG) monoclonal gammopathy. Its clinical symptoms usually respond well to interleukin-1 blockade therapy, which, however, does not impact the underlying monoclonal gammopathy. Herein, we described a female patient who presented with urticarial rash, recurrent fevers, and fatigue for 7 years. Laboratory investigations revealed IgMκ monoclonal protein and

Topics: Adenine; Adult; Antibodies, Monoclonal; Exanthema; Female; Humans; Piperidines; Schnitzler Syndrome; Urticaria

Topics: Adolescent; Anemia; Benzimidazoles; Cyanosis; Exanthema; Humans; Male; Piperidines; Syndrome; Urticaria

Topics: Benzimidazoles; Cetirizine; Chronic Disease; Chronic Urticaria; Humans; India; Piperidines; Urticaria

This was an open-label, single-centre, phase I, bioavailability clinical trial. One drop of the bilastine ophthalmic formulation was administered once daily in each eye of the subjects for 5 days. Bilastine plasma concentrations were measured by HPLC-MS/MS. Adverse drug reactions were recorded for each subject during drug administration and follow-up visits.. Twelve healthy subjects (age 18-55 years) were included in the study. After multiple dose administration, bilastine reached a mean (± SD) maximum blood concentrations of 2682.26 ± 1615.88 pg/mL at a median time of 2.50 h (range 1.25-4.00 h). The half-life of bilastine in plasma was 7.88 ± 6.72 h. Steady state AUC was 19,512.51 ± 9248.76 h·pg/mL. Adverse events were mild and transient, consisting mainly of dysgeusia.. Bilastine once-daily ophthalmic formulation 6 mg/mL is absorbed into the bloodstream in low amounts by the ophthalmic route. The bilastine ophthalmic formulation showed a good safety profile after multiple dose administration.

Topics: Adolescent; Adult; Benzimidazoles; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Piperidines; Tandem Mass Spectrometry; Urticaria; Young Adult

Topics: Area Under Curve; Benzimidazoles; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Models, Biological; Piperidines; Urticaria

Topics: Alopecia; Drug Eruptions; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Urticaria; Young Adult

Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo.. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed.. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria.. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine.. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Topics: Aged; Aged, 80 and over; Benzimidazoles; Conjunctivitis, Allergic; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Incidence; Male; Piperidines; Prospective Studies; Rhinitis, Allergic; Spain; Urticaria

Topics: Benzimidazoles; Chronic Disease; Humans; Piperidines; Treatment Outcome; Urticaria

Topics: Anti-Allergic Agents; Benzimidazoles; Chronic Disease; Drug Therapy, Combination; Female; Hepatitis B, Chronic; Humans; Middle Aged; Omalizumab; Piperidines; Prednisone; Urticaria; Viral Load; Viremia

We conducted a retrospective cohort study evaluating the efficacy and usefulness of the addition of lafutidine, a novel histamine H2-receptor antagonist, in treatment of patients with idiopathic chronic urticaria whose disease was not well controlled with histamine H1-receptor antagonists. Based on the assessment of global improvement, moderate or better improvement was achieved in 39 of 46 patients (85%) after 1-3 weeks of additional administration of lafutidine and 35 patients (76%) after 3 months. No incidence of drug-related adverse reactions was reported in any patient. Lafutidine was rated as useful or better in 34 patients (74%) after 3 months of treatment. The usefulness of the drug was not affected by differences in background factors, such as disease duration, previous treatment duration and the number of concomitant H1-receptor antagonists. Lafutidine appears to be a promising addition to histamine H1-receptor antagonist therapy for the treatment of chronic urticaria resistant to treatment with H1-receptor antagonists alone.

Topics: Acetamides; Adolescent; Adult; Aged; Chronic Disease; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Male; Middle Aged; Piperidines; Pyridines; Retrospective Studies; Urticaria; Young Adult

Topical insect repellent is commonly used throughout the world. Active ingredients typically include N,N-diethyl-meta-toluamide (DEET) or picaridin. Reactions to topical repellents have ranged from contact dermatitis to urticaria. Exposure to DEET can produce contact urticaria; however, it is unknown if patients with a sensitivity to DEET can tolerate picaridin. We report the case of a 22-year-old man who presented for evaluation of contact urticaria that had developed immediately after the application of insect repellent and contact with individuals who had used DEET-containing repellents. No systemic manifestations were noted. Commercially available products containing DEET or picaridin were used for open patch testing. The patient showed immediate urticarial responses to 7% DEET and 7% DEET in ethanol, but patch tests for 5% picaridin and 5% picaridin in ethanol were negative. Based on these results, we conclude that insect repellents containing picaridin may be acceptable alternatives in patients who demonstrate sensitivity to products containing DEET.

Topics: Adult; DEET; Humans; Insect Repellents; Male; Patch Tests; Piperidines; Urticaria; Young Adult

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Topics: Administration, Oral; Benzimidazoles; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

Urticaria is mainly caused by mast cell-derived histamine through the histamine H(1) receptor. Antihistamines are occasionally used on demand upon a recurrence of urticaria; therefore, rapidly acting agents should be explored. The onset of action is assumed to depend on time to maximum concentration (T(max)), but the speed of action needs to be evaluated not only through blood concentration analysis but also by measuring in vivo effectiveness.. In this study, we chose two representative second-generation antihistamines (bepotastine and fexofenadine) with relatively short T(max) values and evaluated their effects on histamine-induced skin responses using both visual and laser Doppler imaging scales.. Suppression of histamine-induced flare and itch was observed 3 and 6 h after administration of both antihistamines. Attenuation of itch was seen 30 min after the administration of each drug and thereafter until 6 h. In addition, bepotastine suppressed flare formation after only 30 min following application.. These results suggest that antihistamines suppress histamine-induced itch and flare, followed by wheal formation, and that bepotastine suppresses skin symptoms sooner after administration than fexofenadine does, which is relatively consistent with the T(max) results.

Topics: Adult; Female; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Pruritus; Pyridines; Skin; Terfenadine; Urticaria

H1-antihistamines are probably the most frequently used drugs in allergic diseases, with widely established efficacy, tolerance, and safety. We report a patient with urticaria due to ingestion of ebastine and fexofenadine. Skin prick tests, patch tests, and basophil activation tests with the implicated drugs and antihistamines from other families were negative. The oral challenges with the implicated antihistamines and other antihistamines tested were positive, but the patient tolerated an oral challenge with cetirizine. We present a patient with urticaria induced by different antihistamines in whom the diagnosis was established by oral challenge. The mechanism of sensitization remains unclear.

Topics: Administration, Oral; Butyrophenones; Diagnosis, Differential; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Piperidines; Terfenadine; Urticaria

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

H(1)-antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H(1)-antihistamines. However, a few cases of H(1)-antihistamine-induced urticaria have been reported. A 34-year-old woman presented with a 4-month history of recurrent urticaria, which was prominently exacerbated by the administration of H(1)-antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one-fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H(1)-antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E-mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H(1)-antihistamine-induced urticaria may have been due to cross-reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H(1)-antihistamines should be considered when urticarial lesions worsen after H(1)-antihistamine treatment.

Topics: Administration, Oral; Adult; Drug Eruptions; Female; Histamine; Histamine H1 Antagonists; Humans; Immunologic Tests; Leukotriene B4; Loratadine; Piperidines; Pyridines; Skin Tests; Terfenadine; Urticaria

Topics: Adult; Cholinesterase Inhibitors; Donepezil; Female; Hand Dermatoses; Humans; Indans; Nurses; Occupational Exposure; Patch Tests; Piperidines; Urticaria

Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Butyrophenones; Cetirizine; Child; Chlorpheniramine; Dermatitis, Atopic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Imidazoles; Japan; Male; Middle Aged; Olopatadine Hydrochloride; Pain Measurement; Piperidines; Population Surveillance; Psychomotor Performance; Pyridines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Surveys and Questionnaires; Terfenadine; Urticaria

H1-antihistamines are commonly used drugs, and probably the most frequently used for allergic diseases. They are pharmacologic inverse agonists of histamine at H1 receptor sites and try to shift the equilibrium of this receptor toward the inactive state, preventing H1 response. A wide variety of adverse effects have been attributed to antihistamines, and they can exceptionally induce skin reactions. We report the case of a patient with several episodes of urticaria induced by different families of antihistamines - piperazines and piperidines. We performed skin prick tests (SPT), patch tests and oral challenges to different antihistamines. We found positive SPT to some antihistamines, and positive oral challenge in others with negative SPT. The route of sensitization remained unclear, and our patient could not finally tolerate any antihistamine after the oral challenges we performed. We support the hypothesis that antihistamines may shift the H1 histamine receptor to the active conformation instead of the inactive conformation, prompting adverse reactions after dosing. This is the first report of urticaria induced by different antihistamines in the same patient with positive SPT to several others.

Topics: Adult; Conjunctivitis; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Humans; Piperazines; Piperidines; Rhinitis; Urticaria

Topics: Arrhythmias, Cardiac; Butyrophenones; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis; Treatment Outcome; Urticaria

Topics: Butyrophenones; Electrocardiography; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Urticaria

Topics: Adult; Aged; Drug Therapy, Combination; Female; Humans; Ketotifen; Male; Middle Aged; Piperidines; Terbutaline; Thiophenes; Urticaria

Topics: Acute Disease; Age Factors; Child, Preschool; Diagnosis, Differential; Exanthema; Gels; Histamine H1 Antagonists; Humans; Meningoencephalitis; Piperidines; Psychoses, Substance-Induced; Urticaria

Topics: Dermatitis, Contact; Drug Eruptions; Female; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity; Male; Piperidines; Urticaria

Topics: Anti-Allergic Agents; Hyperthermia, Induced; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Tripelennamine; Urticaria