Solubility Enhancement of Ebastine by Formulating Microemulsion Using D-Optimal Mixture Design: Optimization and Characterization.

Ebastine, a histamine H1 antagonist, nonsedating, belonging to BCS class II is used in the treatment of allergic rhinitis and chronic idiopathic urticaria. The current study was intended in augmenting the aqueous solubility and dissolution rate of ebastine, by formulating a microemulsion system using oleic acid, Transcutol® HP, and Tween®80 as oily phase, cosurfactant, and surfactant, respectively, by the phase titration method. A custom mixture design with optimality D was used to design the formulation by using the Design Expert® Software (Version 11; Stat-Ease, Inc., Minneapolis, MN, USA). Optimization of formulation was performed using the numerical optimization technique, where optimization is based upon the desirability. The optimized formulation was evaluated for transmittance, viscosity, globule size, polydispersity index, zeta potential, drug content, morphological studies, and in vitro studies. The optimized formulation displayed percent cumulative drug release, ranging from 82.9% to 90.6% obtained after dissolution studies and the percent cumulative drug release after diffusion studies ranged from 83.3% to 100%. The in vitro release data were subjected to kinetic treatment. The zero-order and first-order plots were linear and showed the highest values for R2, which indicated mixed-order release. The Higuchi plot was linear, indicating diffusion as the mechanism of release. From Peppas plot, it was further confirmed that the release for dissolution studies was anomalous and for diffusion studies it was zero order. Thus, the studies concluded that the microemulsion technique is a very good approach for enhancing the solubility and dissolution rate of the BCS class II drug ebastine.

Urticária aquagênica: relato de caso e revisão de literatura / Aquagenic urticaria: a case report and literature review

A urticária aquagênica é uma forma rara de urticária crônica induzida (UCInd) desencadeada por um estímulo específico. A patogênese não é totalmente compreendida, mas os sintomas se iniciam minutos após a exposição cutânea à água, independentemente de sua temperatura, e as urticas têm o padrão foliculocêntricas. O diagnóstico é confirmado através do teste de provocação, e o tratamento de primeira linha são os anti-histamínicos de segunda geração. Neste artigo, relatamos um caso de urticária aquagênica e fazemos uma breve revisão da literatura sobre o tema.

Aquagenic urticaria is a rare form of chronic inducible urticaria (CIndU) triggered by a specific stimulus. Pathogenesis is not fully understood, but symptoms appear minutes after cutaneous exposure to water, regardless of temperature, and wheals have a folliculocentric pattern. The diagnosis of CIndU is confirmed by provocation testing using established protocols, and first-line treatment is second-generation antihistamines. In this article, we report a case of aquagenic urticaria and provide a brief review of the relevant literature.

Clinical difference between single subtype and mixed subtype chronic urticaria: A retrospective study.

BACKGROUND: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. AIMS: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. METHODS: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. RESULTS: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. LIMITATIONS: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. CONCLUSION: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients.

Use of Azelastine and Sodium Chloride Spray for Prevention of Sinusitis in ICU Admitted Patients: A Randomized Clinical Trial.

BACKGROUND: Nosocomial sinusitis is a common and less attended complication in patients admitted to intensive care units (ICU). It can cause several problems, such as prolongation of hospitalization, comorbidity, and mortality in patients. The present study aimed to evaluate the effect of azelastine (second-generation antihistamine) and sodium chloride spray on sinusitis prevention in ICU admitted patients. METHODS: In this randomized, open-label, and parallel clinical trial a total of 126 patients were enrolled (63 patients per arm). Finally, 121 patients (61 patients in the control group and 60 patients in the treatment group) completed the study, and 120 patients entered the final analysis. In the treatment group, during 24 h after the insertion of nasogastric tube azelastine and sodium chloride sprays were administered (one puff from each spray every 12 h) while no intervention was conducted in the control group. Primary and secondary end-points were evaluated within 10 days of the study period. RESULTS: The incidence of sinusitis and pneumonia (18.3% and 16.6% in the control group compared to 8.3% and 3.3% in the treatment group, respectively) in the treatment group showed a decreasing trend; however, only the difference of pneumonia was statistically significant between groups (P = 0.03). In addition to the clinical pulmonary infection score, nasal and tracheal secretions were significantly improved in the treatment group (P = 0.03, P < 0.001, and P = 0.01, respectively). CONCLUSIONS: The findings of the present study offer an inexpensive, low-risk, and efficacious intervention for the prevention of upper respiratory tract infections in ICU patients.

Improved survival in several cancers with use of H1-antihistamines desloratadine and loratadine.

BACKGROUND: We have previously shown an association with substantially improved survival in breast cancer and melanoma for desloratadine and loratadine users, and set out to find whether an improved survival can be seen in tumors with and without a known response to immune checkpoint therapy, such as anti-CTLA-4 or anti-PD-1. METHODS: We investigated survival and use of six common H1-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) in a nation-wide cohort of all 429,198 Swedish patients with ten types of immunogenic (gastric, colorectal/anal, pancreatic, lung, breast, prostate, kidney, and bladder cancer, melanoma and Hodgkin lymphoma) and six non-immunogenic (liver, uterine, ovarian, brain/CNS, and thyroid cancer and non-Hodgkin lymphoma) tumors diagnosed 2006-2017. Follow-up was until 2019-02-24. FINDINGS: Desloratadine use was associated with an improved survival for all immunogenic tumors, but not for the non-immunogenic ones. Loratadine use was associated with improved survival for some tumors. Use of the other antihistamines could not be shown to be consistently associated with improved survival to a statistically significant degree. INTERPRETATION: Our hypothesis is that our findings result from immune checkpoint inhibition, and we believe both desloratadine and loratadine should be tested in randomized clinical trials as treatment of immunogenic tumors, with priority given to trials of desloratadine as treatment of tumors with few therapy options and dismal prognoses, such as pancreatic cancer. If our results can be confirmed in a clinical setting, new, potentially curative, therapies could result for several tumors, including ones with dire prognoses and limited treatment options.

Misuse and dependence of dimenhydrinate: A mixed studies systematic review.

BACKGROUND: Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been reports of potential DMH tolerance and dependence and a possible euphoric potential accompanying heavy use (>100 mg/day). Despite the potential for misuse, there is a gap in the literature concerning patterns, characteristics, and potential mechanisms of DMH misuse. AIMS: This review aimed to synthesize evidence on the pharmacology, clinical effects, and management of DMH misuse and dependence to inform clinical decision making and relevant drug policy. METHODS: We conducted a systematic review in accordance with the PRISMA guidelines and using Cochrane collaboration methods. We searched seven databases from their inception through July 2019. To be included in the review, studies needed to measure or focus on one or more dimensions of morbidity or mortality related to the misuse of DMH. Quantitative, qualitative and mixed-method studies were included in order to capture the breadth of possible studies. Studies were excluded if they did not fit into the conceptual framework of the study of if they focused primarily on the misuse of other substances. A narrative synthesis of study findings was pursued given the limited capacity for a quantitative meta-analysis. FINDINGS: We identified 24 studies, which described a range of neuropsychiatric sequelae related to DMH consumption, including seizures, psychosis, depression, intoxication (resembling anticholinergic syndrome) and withdrawal. The sedative and euphoric properties, readily available nature, and low cost of DMH appear to facilitate DMH dependence, which were more commonly reported among individuals who had concurrent psychiatric disorders, displaying symptoms such as low motivation, poor concentration, and delirium. The overall quality of studies identified by this review was low-largely because the majority of studies were case reports or review articles, with few intervention or cohort studies. CONCLUSIONS: There is some evidence to suggest the existence of DMH-related syndromes involving intoxication, withdrawal, and dependence, more commonly among long-term, heavy DMH consumers. However, higher quality studies are needed to confirm preliminary findings that there may be a biological basis for such syndromes.

Second-generation antihistamines: a study of poisoning in children.

Background and objectives: The toxicity of second-generation antihistamines after an overdose by a child is still unknown. The objective of this study is to use data from Poisons Centres in France to describe the toxicity profile of second-generation antihistamines for children and to compare the severity of poisoning observed from these with a first-generation antihistamine.Method: This was a retrospective, multi-centre and observational study focusing on human cases of single-substance exposure to a second-generation antihistamine and to mequitazine, reported between 1 January 2001 and 31 December 2016 in Poisons Centres in France.Results: From a total of 9403 children included, 5980 were exposed to a second-generation antihistamine and 3423 were exposed to mequitazine. The severity of exposure to second-generation antihistamines in children is low: among the children followed until a known outcome, 9% of children were symptomatic and in 97% of cases, the symptoms shown were of a minor-level severity (primarily drowsiness or restlessness). Depending on the substance, children who ingested doses 16 to 69 times the maximum recommended therapeutic dose remained asymptomatic. No deaths or severe symptoms were observed. No cases of lengthening of the QT interval or arrhythmias were identified. Mequitazine led to more symptoms than other substances (14.8% symptomatic children vs. 7.5%, Odd ratio (OR): 2.3 (2.0-2.6), p < 0.0001), more symptoms of moderate intensity (1.4 vs. 0.2%, OR: 8.3 (4.1-18.5), p < 0.0001) and more hospitalisation (19.1 vs. 8.7%, OR: 2.5, 95% CI: (2.2-2.8), p < 0.0001).Conclusion: The severity of poisoning from second-generation antihistamines appears to be low among children and considerably lower than poisoning caused by mequitazine.

Structural and clinical impact of anti-allergy agents: An overview.

Allergic disorders are markedly rising in industrialized countries. The identification of compounds that trigger the immunoglobulin E (IgE)-dependent allergic reaction remain the means to improve the quality of life by limiting patient's exposure to critical allergens. Information concerning the treatment and onset of allergic disorders including atopic dermatitis, allergic rhinitis, and bronchial asthma has been provided by the research over the past decade. Recent studies also indicated that allergic inflammation is associated closely with their exacerbation and progression and indeed is the basic pathophysiology of allergic diseases. As a result of immunological and molecular biological studies our understanding of the mechanism of allergic inflammation with regard to therapeutic agents has improved. While much effort has been paid to developing a new anti-allergic agent, the allergic disease has yet to be completely conquered. The more extensive research will allow the development of new therapeutics to combat allergic diseases. Currently, with respect to mechanism of action anti-allergy drugs are classified into five types including histamine H1 antagonists, leukotriene antagonists, Th2 cytokine inhibitors, thromboxane A2 inhibitors and mediator-release inhibitors. The use of two or more anti-allergy agents together is not acknowledged at present, but this will be the subject of research in the future because with different mechanisms of action anti-allergy agents used at the same time will theoretically increase their effects. This review article focuses on anti-allergy agents highlighting their applications, clinical trials and recent advancement on drugs.

Synergistic Effect of H1-Antihistamines on Topical Corticosteroids for Pruritus in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Although oral antihistamines (H1-histamine receptor antagonists) are the main treatment option for pruritus in general skin dermatosis, their effect in treating pruritus of atopic dermatitis (AD) has not yet been established. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effectiveness of combined therapy of H1-antihistamines and topical steroids. METHODS: We systematically searched MEDLINE, Embase, and CENTRAL databases for articles published from 1967 to 2015. We identified 1,206 studies and assessed their titles, abstract, and full-text. Random effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI). RESULTS: Two studies satisfying the inclusion criteria of antihistamine therapy with mandatory topical steroid use were selected. Comparing antihistamine monotherapy with combination therapy, patients treated with the addition of antihistamine to topical corticosteroids showed a statistically significant clinical improvement (standard MD, -0.24; 95% CI, -0.42 to -0.05; p=0.01). CONCLUSION: H1-antihistamines may have a synergistic effect when combined with topical steroids by influencing various associative factors of chronic pruritus in AD.

Effect of clemastine fumarate on TLR4/PI3K/Akt signaling pathway during hypoxia-reoxygenation in rat cardiomyocytes / 中华麻醉学杂志

Objective To evaluate the effect of clemastine fumarate on Toll-like receptor 4/phosphatidylinositol-3-kinase/serine-threonine kinase (TLR4/PI3K/Akt) signaling pathway during hypoxia-reoxygenation (H/R) in rat cardiomyocytes.Methods H9C2 cells of rats cultured in vitro were seeded in culture wells or dishes at a density of 1×105 cells/ml and divided into 3 groups (n=11 each) by using a random number table method:control group (group C),H/R group and clemastine fumarate group (CF group).Cardiomyocytes were exposed to 5％ CO2-95％ N2in a low-glucose DMEM medium at 37℃ for 4 h followed by 4 h reoxygenation.At 4 h of reoxygenation,the cell viability was detected by CCK-8 assay,the ultrastructure was observed with a transmission electron microscope,the expression of TLR4,PI3K,phosphorylated Akt (p-Akt) and caspase-3 was detected by Western blot,and the expression of TLR4,PI3K and caspase-3 was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the expression of TLR4 and caspase-3 was up-regulated,and the expression of PI3K and p-Akt was down-regulated in group H/R (P＜0.05).Compared with group H/R,the cell viability was significantly increased,the expression of TLR4 and caspase-3 was down-regulated,the expression of PI3K and p-Akt was up-regulated (P＜0.05),and the mitochondrial damage was significantly attenuated in group CF.Conclusion The mechanism by which clemastine fumarate alleviates H/R injury to rat cardiomyocytes may be related to inhibiting TLR4 expression and activating PI3K/Akt signaling pathway.

Synergistic Effect of H1-Antihistamines on Topical Corticosteroids for Pruritus in Atopic Dermatitis: A Systematic Review and Meta-Analysis

BACKGROUND: Although oral antihistamines (H1-histamine receptor antagonists) are the main treatment option for pruritus in general skin dermatosis, their effect in treating pruritus of atopic dermatitis (AD) has not yet been established. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effectiveness of combined therapy of H1-antihistamines and topical steroids. METHODS: We systematically searched MEDLINE, Embase, and CENTRAL databases for articles published from 1967 to 2015. We identified 1,206 studies and assessed their titles, abstract, and full-text. Random effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI). RESULTS: Two studies satisfying the inclusion criteria of antihistamine therapy with mandatory topical steroid use were selected. Comparing antihistamine monotherapy with combination therapy, patients treated with the addition of antihistamine to topical corticosteroids showed a statistically significant clinical improvement (standard MD, −0.24; 95% CI, −0.42 to −0.05; p=0.01). CONCLUSION: H1-antihistamines may have a synergistic effect when combined with topical steroids by influencing various associative factors of chronic pruritus in AD.

Optimal Doses of H1 Antihistamines Do Not Increase Susceptibility to Febrile Convulsions in Children.

BACKGROUND: The purpose of this study was to elucidate whether H1 antihistamine administration increases susceptibility to febrile convulsions in children. METHODS: A single-center, retrospective observational study was conducted in Japan. The study included 380 children with febrile convulsions between the ages of six months and five years transported via ambulance from 2011 through 2016. They were divided into the preseizure H1 antagonist "use group" and the "nonuse group." The former consisted of children who took H1 antagonists within 24 hours before the seizure onset. The primary outcome (seizure duration) and the secondary outcome (interval from fever to seizure onset) were compared between the two groups. RESULTS: Of the 380 study patients, 70 (18%) were identified as the use group. None of the patients was taking excessive doses of H1 antagonists. The prevalence of seizures lasting 15 minutes or longer was not different between the use group and the nonuse group (11% versus 8%, prevalence ratio 1.47 [95% confidence interval, 0.63 to 3.42], P = 0.37). The prevalence of fever to seizure onset less than six hours was significantly lower in the use group (26% versus 52%, prevalence ratio 0.33 [95% confidence interval 0.19 to 0.60], P < 0.001). Similar results were obtained when analyses were conducted separately by different generations (first and second) of H1 antagonists. CONCLUSIONS: Prolonged seizure duration and shortened interval from fever to seizure were not observed in children who received H1 antagonists. This study provides evidence that H1 antagonists at optimal doses could be safely used in febrile children with allergic symptoms.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

[Chronic urticaria in childhood : Rational diagnostics and treatment]. / Chronische Urtikaria im Kindesalter : Rationale Diagnostik und Therapie.

Chronic urticaria (CU) is defined by episodes of urticaria with or without angioedema, which recur daily or nearly daily over more than 6 weeks. Sudden manifestations of CU with or without known causes are termed chronic spontaneous urticaria, which is differentiated from chronic inducible urticaria. The differential diagnoses of CU in childhood range from self-limiting dermatoses to severe systemic diseases. Further targeted steps are taken to detect potential trigger factors or underlying illnesses only if suspicion arises on anamnestic grounds and CU is best treated in accordance with international guidelines. First-line therapy consists of non-sedating H1-antihistamines at approved or even higher doses. If symptoms persist, additional treatment with omalizumab, cyclosporine or montelukast can be initiated after careful individual consideration.

Evidence for the hERG Liability of Antihistamines, Antipsychotics, and Anti-Infective Agents: A Systematic Literature Review From the ARITMO Project.

A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to compare it with current clinical risk of torsade de pointes (TdP). Eligible studies were hERG assays reporting half-minimal inhibitory concentrations (IC50). A "hERG safety margin" was calculated from the IC50 divided by the peak human plasma concentration (free Cmax ). A margin below 30 defined hERG liability. Each drug was assigned an "uncertainty score" based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (www.credibledrugs.org). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty-one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti-infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. This may be due to gaps in clinical evidence, limitations of hERG/Cmax data, or other patient/drug-specific factors that contribute to real-life TdP risk.

Efficacy of clemastine fumarate in antagonizing atracurium-induced release of histamine in patients undergoing surgery under general anesthesia / 中华麻醉学杂志

Objective To evaluate the efficacy of clemastine fumarate in antagonizing atracuriuminduced release of histamine in the patients undergoing surgery under general anesthesia.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 21-59 yr,with body mass index of 17-26 kg/m2,scheduled for elective modified radical mastectomy,were divided into 2 groups (n=40 each) using a random number table:control group (group C) and clemastine fumarat group (group CF).Clemastine fumarate 2 mg was injected intramuscularly at 20 min before induction of anesthesia.Anesthesia was induced with iv midazolam 0.1 mg/kg,etomidate 0.3 mg/kg,fentanyl 4-6 μg/kg and atracurium 0.8 mg/kg.The patients were mechanically ventilated after insertion of the larygeal mask airway.Anesthesia was maintained with inhalation of 2％ sevoflurane.Before administration of clemastine fumarate,at 20 min after administration,immediately before administration of atracurium,and at 2,5,10 and 20 min after administration of atracurium,arterial blood samples were taken for determination of plasma histamine concentrations,and the peak airway pressure and degree of cutaneous color were recorded.The development of histaminemia and adverse cardiovascular events was assessed.Steward recovery scores and Ramsay sedation scores were recorded at 10 min after removal of the laryngeal mask airway.Results The incidence of histaminemia was 60％ and 8％ in C and CF groups,respectively.Compared with group C,the plasma histamine concentrations,incidence of histaminemia,degree of cutaneous color,and incidence of hypotension and tachycardia were significantly decreased (P＜0.05),and no significant change was found in the peak airway pressure,Steward recovery scores and Ramsay sedation scores in group CF (P＞0.05).Conclusion For atracurium-induced release of histamine in the patients undergoing surgery under general anesthesia,clemastine fumarate 2 mg injected intramuscularly before operation can not only antagonize histamine at H1 level,but also reduce histamine release,and exerts no influence on recovery from anesthesia and produces good antihistamine efficacy.

Efficacy of fexofenadine hydrochloride tablets at tapering doses for the treatment of chronic spontaneous ;urticaria:a clinical observation / 中华皮肤科杂志

Objective To evaluate the efficacy of fexofenadine hydrochloride tablets at tapering doses for the treatment of chronic spontaneous urticaria. Methods After receiving evaluation of medical history and undergoing autologous serum skin test (ASST), 80 patients with chronic spontaneous urticaria were randomly divided into two groups:conventional dose group administrating fexofenadine hydrochloride tablets 120 mg/d for 12 consecutive weeks, tapering dose group administrating fexofenadine hydrochloride tablets 120 mg/d for the first 4 weeks followed by dose tapering of fexofenadine hydrochloride tablets by 30 mg at the 5th and 9th weeks. The urticaria activity score(UAS) and dermatology life quality index(DLQI)were evaluated before the treatment(baseline)as well as after 4?, 8?and 12?week treatment, and the total dose of fexofenadine hydrochloride was calculated. Results A total of 76 patients completed the 12?week treatment, including 37 patients in the conventional dose group and 39 patients in the tapering dose group. After 4?, 8?and 12?week treatment, a significant decrease was observed in the UAS in the conventional dose group(0.64 ± 0.82, 0.37 ± 0.68 and 0.27 ± 0.56 vs. 4.08 ± 0.79, all P0.05). After 8?and 12?week treatment, symptoms were controlled in 71.79%(28/39)and 82.05%(32/39)of patients in the tapering dose group, respectively, with the total dose of fexofenadine hydrochloride being significantly lower in the tapering dose group than in the conventional dose group (both P<0.001). Conclusion After 4- 8 weeks of treatment with fexofenadine hydrochloride, the tapering dose regimen and conventional dose regimen show similar clinical efficacy in patients with chronic spontaneous urticaria.

Application of antihistamines in special populations / 中华皮肤科杂志

Antihistamines,a group of drugs most commonly used for the treatment of allergic diseases in dermatology,exert favorable efficacy and are well tolerated in most people.Due to their wide application,the safety of medication is particularly important.When they are used in some special populations with allergic diseases,such as children,pregnant and lactating women,the elderly and people with hepatic or renal insufficiency,their pharmacodynamics,metabolic characteristics and interactions with other drugs should be fully considered,and profits of medication and potential adverse effects should be well weighed before choosing relatively safe antihistamines.In addition,decreasing the routine dose or prolonging intervals between the administration of antihistamines may also be attempted to achieve maximum safety.

Double-blind placebo-controlled study of bepotastine besilate in pediatric patients with perennial allergic rhinitis.

BACKGROUND: Although second-generation antihistamines, such as bepotastine besilate, are recommended as a first-line treatment option for adult perennial allergic rhinitis (PAR), few non-sedating second-generation antihistamines are safe for children. OBJECTIVE: A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 - 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline. RESEARCH DESIGN AND METHODS: Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline. RESULTS: Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first-generation antihistamines were reported and no difference in adverse events between groups was observed. CONCLUSIONS: Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 - 15 years, and has a significant clinical impact on PAR. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01861522 ( https://clinicaltrials.gov/ct2/show/NCT01861522 ).