RESUMO
OBJECTIVE: Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria. METHODS: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo. RESULTS: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses. CONCLUSION: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.
Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina , Terfenadina , Terfenadina/análogos & derivados , Terfenadina/farmacocinética , Terfenadina/farmacologia , Terfenadina/administração & dosagem , Humanos , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Urticária/tratamento farmacológicoRESUMO
Through the utilization of fluorescence spectroscopy, electrochemical, and molecular docking methods, this research investigates the interaction between the antihistamine drug desloratadine and calf thymus double-stranded DNA (ct-dsDNA). Deoxyguanosine (dGuo) and deoxyadenosine (dAdo) oxidation signals were diminished by incubation with varying concentrations of desloratadine, as determined by differential pulse voltammetry (DPV). This change was ascribed to desloratadine's binding mechanism to ct-dsDNA. The binding constant (Kb) between desloratadine and ct-dsDNA was determined to be 2.2 × 105 M-1 throughout electrochemical experiments. In order to further develop our comprehension of the interaction mechanism between desloratadine and ct-dsDNA, a series of spectroscopic experiments and molecular docking simulations were conducted. The Kb value was found to be 8.85 × 104 M-1 at a temperature of 25 °C by the use of fluorescence spectroscopic techniques. In summary, the utilization of electrochemical and spectroscopic techniques, alongside molecular docking investigations, has led to the prediction that desloratadine has the capability to interact with ct-dsDNA by groove binding.
Assuntos
DNA , Técnicas Eletroquímicas , Loratadina , Simulação de Acoplamento Molecular , Espectrometria de Fluorescência , Loratadina/análogos & derivados , Loratadina/química , Loratadina/metabolismo , Loratadina/farmacologia , DNA/metabolismo , DNA/química , Bovinos , Animais , Antagonistas não Sedativos dos Receptores H1 da Histamina/metabolismo , Antagonistas não Sedativos dos Receptores H1 da Histamina/químicaRESUMO
Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1 -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H1 -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1 -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.
Assuntos
Carragenina , Cetirizina , Edema , Animais , Cetirizina/farmacologia , Edema/tratamento farmacológico , Edema/induzido quimicamente , Ratos , Masculino , Estereoisomerismo , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Relação Dose-Resposta a Droga , Ratos Wistar , Imidazóis/farmacologia , Ratos Sprague-Dawley , DibenzazepinasRESUMO
BACKGROUND: Our aim was to measure the effectiveness of oral isotretinoin with desloratadine compared with oral isotretinoin alone in treating moderate to severe acne at a tertiary care teaching hospital in North India. In this study, 90 patients with moderate to severe acne were enrolled to participate based on their fulfilling the inclusion criteria. METHODS: A randomized, assessor-blinded, parallel-arm study was conducted. Randomization was done using computer-generated tables to allocate treatments in a 1:1 ratio. A low-dose oral isotretinoin at a dose of 0.3 mg/kg/day with tab desloratadine at 5 mg/day was applied to the study group and compared against the same patients going without the dosage when controls were conducted. Follow-up was at 4, 8, and 12 weeks. RESULTS: The primary outcome was an improved global acne grading system (GAGS) score and decreased acne lesion count. SECONDARY OUTCOME: patient satisfaction with treatment. The 90 participants were randomized and 15 participants dropped out of the study, leaving 75 participants for intention to treat analysis (n = 41, n = 30). At week 12, the GAGS score and acne lesion count between the study and control groups were comparable (P > 0.05). Pruritus reported was 9.76% in the study versus 33.33% in the control group (P = 0.018). Also, 53.66% of participants reported "excellent" treatment satisfaction in the study group versus 36.67% in the control group. CONCLUSIONS: The addition of desloratadine to an isotretinoin regimen has a role in reducing disease and therapy-related pruritus in acne and leads to improved patient satisfaction.
Assuntos
Acne Vulgar , Fármacos Dermatológicos , Isotretinoína , Loratadina , Satisfação do Paciente , Índice de Gravidade de Doença , Humanos , Isotretinoína/administração & dosagem , Isotretinoína/efeitos adversos , Acne Vulgar/tratamento farmacológico , Loratadina/administração & dosagem , Loratadina/análogos & derivados , Loratadina/efeitos adversos , Feminino , Masculino , Administração Oral , Adulto Jovem , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Adolescente , Adulto , Quimioterapia Combinada , Método Simples-Cego , Resultado do Tratamento , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversosRESUMO
International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose when adequate symptom control cannot be achieved with the standard dosage. However, this recommendation is primarily based on expert opinions, and there is a lack of large, well-designed, double-blind clinical trials. Most the existing trials provide insufficient data, and due to the heterogeneity of the conducted trials on antihistamine effects (definition of control, design, quality, lack of an active comparator, no placebo arm, small sample size, outcomes) and their short duration, comparative analysis is challenging. However, it can be concluded that the use of modern second-generation antihistamines is both effective and safe based on the available data and our own long-term experiences in the specialized outpatient clinic of a university dermatology department, even though increased dosages (up to fourfold as per the current international guidelines) may be necessary for symptom control. Another therapeutic option for refractory symptoms in chronic spontaneous urticaria is subcutaneous administration of omalizumab at a dosage of 300â¯mg at 4week intervals as a very safe and effective treatment.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Doença Crônica , Urticária/tratamento farmacológico , Omalizumab/uso terapêutico , Antagonistas dos Receptores Histamínicos H1 , Urticária Crônica/tratamento farmacológico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Prurido/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We describe an unusual presentation of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome in a 15-year-old male, recalcitrant to low-dose anti-histamines, which subsequently responded to high-dose fexofenadine.
Assuntos
Cianose , Terfenadina , Urticária , Humanos , Masculino , Terfenadina/análogos & derivados , Terfenadina/uso terapêutico , Adolescente , Cianose/etiologia , Cianose/induzido quimicamente , Urticária/tratamento farmacológico , Síndrome , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversosRESUMO
BACKGROUND: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment. OBJECTIVE: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU. METHODS: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17. RESULTS: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n = 2649, RR = 1.36, 95%CI:1.30-1.43, p < 0.00001), cure (n = 2649, RR = 1.54, 95%CI:1.42-1.66, p < 0.00001) and recurrence (n = 446, RR = 0.34, 95%CI:0.20-0.58, p < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n = 2317, RR = 0.76, 95% CI:0.59-0.97, p = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported. CONCLUSIONS: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.
Assuntos
Urticária Crônica , Ácido Glicirrízico , Antagonistas não Sedativos dos Receptores H1 da Histamina , Humanos , Doença Crônica , Urticária Crônica/tratamento farmacológico , Ácido Glicirrízico/efeitos adversos , Ácido Glicirrízico/uso terapêutico , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêuticoRESUMO
OBJECTIVE: Although second-generation antihistamines have reduced sedation-related side effects compared to first-generation antihistamines, sedation may still impair motor vehicle driving performance. Moreover, receiving/making phone calls using a hands-free function can negatively affect driving performance. Therefore, herein, driving performance was evaluated using a driving simulator to gain insights into the hazards of driving by combining second-generation antihistamines and a calling task, i.e., simulated calls using a hands-free function. METHODS: In this study, 20 subjects drove in a driving simulator in the absence or presence of a calling task while taking or not taking second-generation antihistamines. Driving performances for nonemergency and emergency events were determined, and a comparative analysis of intra-individual variability when taking and not taking second-generation antihistamines was conducted. RESULTS: First, when nonemergency and emergency were examined in the absence of a calling task, no significant difference in driving performance was observed between taking and not taking second-generation antihistamines. Next, when the nonemergency event was examined in the presence of a calling task, no significant difference in driving performance was observed between taking and not taking second-generation antihistamines. However, when the emergency event was examined in the presence of a calling task, a significant difference in driving performance was observed between taking and not taking second-generation antihistamines, thus resulting in reduced driving performance. CONCLUSIONS: The new system with added calling tasks allowed the extraction of the potential risks of driving performance of second-generation antihistamines that may have been previously overlooked. This study suggests that pharmacists and other healthcare professionals may need to instruct people taking any second-generation antihistamine to focus on driving and not on subtasks that require cognitive load such as talking while driving.
Assuntos
Condução de Veículo , Antagonistas não Sedativos dos Receptores H1 da Histamina , Humanos , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Acidentes de Trânsito , Antagonistas dos Receptores Histamínicos/efeitos adversosRESUMO
Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment.
Assuntos
Asma , Antagonistas não Sedativos dos Receptores H1 da Histamina , Rinite Alérgica Sazonal , Rinite Alérgica , Humanos , Criança , Qualidade de Vida , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Alérgenos/uso terapêutico , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Dessensibilização Imunológica , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêuticoRESUMO
Fexofenadine hydrochloride (HCl) is a second-generation, nonsedating, histamine H1-receptor antagonist used to manage seasonal allergic rhinitis and chronic idiopathic urticaria. A new oral pediatric suspension of fexofenadine HCl has been developed, with the preservative potassium sorbate replacing parabens. The objective of this phase 1 single-center, open-label, randomized, 2-treatment, full-replicated, 4-period, 2-sequence crossover study in healthy adult volunteers was to assess the bioequivalence of 30 mg of the new oral suspension of fexofenadine HCl (test) versus 30 mg of the marketed pediatric oral suspension of fexofenadine HCl (reference). The replicate design was based on the high intra-individual variability of fexofenadine (>30% on Cmax ). The study comprised 68 randomized and treated volunteers. Plasma concentrations of fexofenadine were similar following the administration of a single dose of each formulation. Cmax , AUClast , AUC, median tmax , and mean t1/2z were similar between administrations of the same fexofenadine formulation and between formulations. A high intra-individual variability was confirmed with both formulations. Bioequivalence of the test and reference fexofenadine HCl formulations was demonstrated as the 90% confidence intervals of the geometric least squares mean ratio for Cmax , AUClast , and AUC of fexofenadine were all within the bioequivalence range of 0.80-1.25. There were no serious adverse events (AEs) or study discontinuations due to treatment-emergent AEs with either fexofenadine HCl formulation. The new paraben-free fexofenadine HCl 30-mg oral suspension and marketed fexofenadine HCl 30-mg pediatric oral suspension are bioequivalent under fasting conditions, with no safety concerns and a safety profile consistent with the known profile of fexofenadine.
Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina , Terfenadina , Adulto , Humanos , Criança , Equivalência Terapêutica , Estudos Cross-Over , Terfenadina/efeitos adversos , Antagonistas dos Receptores Histamínicos H1 , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversosRESUMO
BACKGROUND: The daytime tiredness experienced by the vast majority of allergic rhinitis (AR) sufferers is directly related to the fact that they experience disrupted sleep at night. This study compared the effects of recently marketed second-generation H1 antihistamines (SGAs) on nighttime sleep and daytime sleepiness in patients with AR, with patients grouped into those taking non-brain-penetrating antihistamines (NBP group) and those taking brain-penetrating antihistamines (BP group). METHODS: Patients with AR completed self-administered questionnaire-based surveys to determine Pittsburgh Sleep Quality Index (PSQI) before and after taking SGAs. Statistical analysis was performed on each evaluation item. RESULTS: Of 53 Japanese patients with AR between 6 and 78 years old, median (SD) age was 37.0 (22.4) years old and 21 were men (40%). Of the 53 patients, 34 were the NBP group and 19 were the BP group. In the NBP group, mean (SD) subjective sleep quality score after medication was 0.76 (0.50), which was significantly lower (better) than the score of 0.97 (0.52) before medication (p = 0.020). In the BP group, mean (SD) subjective sleep quality score after medication was 0.79 (0.54), which was not significantly different from the score of 0.74 (0.56) before medication (p = 0.564). In the NBP group, mean (SD) global PSQI score was 3.47 (1.71) after medication, which was significantly lower (better) than the score of 4.35 (1.92) before medication (p = 0.011). In the BP group, mean (SD) global PSQI score was 2.47 (2.39) after medication, which was not significantly different from the score of 3.00 (2.71) before medication (p = 0.125). CONCLUSION: Subjective sleep quality and global PSQI score were improved only in the group taking non-brain-penetrating SGAs.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Antagonistas não Sedativos dos Receptores H1 da Histamina , Rinite Alérgica , Masculino , Humanos , Adulto , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Sono , Fadiga , Rinite Alérgica/tratamento farmacológicoRESUMO
BACKGROUND: Allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities, and quality of life. Non-sedating second-generation H1-antihistamines are the first-line treatment of choice. Aim of the study was to define the role of bilastine among second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria in patients of different ages. METHODS: An international Delphi study was carried out to assess consensus among experts from 17 European and extra-European countries on three main topics: 1) Burden of disease; 2) Current treatment options; 3) Specific characteristics of bilastine among second-generation antihistamines. RESULTS: Here, we present the results obtained for a selection of 15 out of 27 consensus statements, focused on disease burden, role of second-generation antihistamines and bilastine profile. The rate of concordance was ≥98% for 4 statements, ≥ 96% for 6, ≥ 94% for 3, and ≥90% for 2. CONCLUSIONS: The high degree of agreement obtained suggests a wide awareness of the burden of allergic rhinoconjunctivitis and chronic urticaria among experts from all over the world and reflects a broad consensus on the role of second-generation antihistamines in general and of bilastine in particular for their management.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Qualidade de Vida , Técnica Delphi , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêuticoRESUMO
BACKGROUND: Standard doses of second-generation H1-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence an increase in the dose of sgAHs is recommended. However, literature evaluating the efficacy and safety of this treatment remains inconclusive, highlighting the need for a systematic review and meta-analysis. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of high-dose sgAHs compared with standard-dose sgAHs in treating CSU. METHODS: A systematic literature search of double-blind, randomized controlled trials (RCT) utilizing multiple doses of sgAHs was performed by searching the electronic databases Medline, Embase, PsycInfo, Cochrane databases, and Web of Science. Bibliographies were also manually searched. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The response rate, the number of adverse events, somnolence, and withdrawal due to adverse events were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. RevMan (V5.3) software was used for data synthesis. RESULTS: A total of 13 studies were identified, seven of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that high-dose sgAHs was associated with a significantly higher response rate than standard-dose (RR 1.13, 95% CI 1.02 to 1.26; P = 0.02). Conversely, high doses of sgAHs were associated with significantly higher somnolence rates than standard dose (RD 0.05, 95% CI 0.01 to 0.09; P = 0.02). There was no significant difference in adverse events or withdrawal due to adverse events between standard- and high-dose treatments. CONCLUSIONS: Our analyses showed that a high dose of sgAHs (up to two times the standard dose) might be more effective than a standard dose in CSU treatment. High-dose and standard-dose sgAHs showed similar adverse events, except for somnolence, where incidence was found to be dose-dependent in some studies. However, given the limited number of studies, our meta-analysis results should be interpreted with caution.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Humanos , Sonolência , Ensaios Clínicos Controlados Aleatórios como Assunto , Urticária Crônica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêuticoRESUMO
Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Estudos Prospectivos , Qualidade de Vida , Cetirizina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Urticária/diagnóstico , Urticária/tratamento farmacológico , Urticária Crônica/tratamento farmacológicoRESUMO
BACKGROUND: The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated. OBJECTIVE: To compare the safety profiles of individual sgAHs and/or dosing regimens in adolescents or adult patients with CU using a systematic review and network meta-analysis of all available evidence. METHODS: With limited English publications, electronic databases and gray literature were searched for randomized clinical trials from inception, with searches last updated on January 20, 2023. Relevant safety outcomes included treatment unacceptability (all-cause discontinuation), tolerability (discontinuation due to any adverse events), adverse events, serious adverse events, central nervous system (CNS) side effects, and anticholinergic side effects. Regarding the network estimates, the probability of being associated with the highest adverse outcome risk was estimated for each treatment comparison. RESULTS: Fifty-one randomized clinical trials with 14 individual sgAHs and different dosing regimens, involving 7502 participants, were included. On the basis of the findings from network meta-analyses, variations in sgAH treatment comparisons were observed regarding the unacceptability of treatment, tolerability, adverse events, and CNS side effects. There were no statistically significant differences between the results of sgAH treatment for serious adverse events and those for anticholinergic side effects. On the basis of the ranking of safety profiles, emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the top 3 ranked treatments with unfavorable safety profiles associated with CNS side effects and any adverse events. CONCLUSIONS: These findings suggest evidence of variations in safety profiles among sgAHs for CU treatment, particularly in terms of adverse events and CNS side effects.
Assuntos
Urticária Crônica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antagonistas não Sedativos dos Receptores H1 da Histamina , Adulto , Humanos , Adolescente , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Urticária Crônica/tratamento farmacológico , Antagonistas ColinérgicosRESUMO
This publication is the second part of the German-language S3 guideline on urticaria. It covers the management of urticaria and should be used together with Part 1 of the guideline on classification and diagnosis. This publication was prepared according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system conditions in German-speaking countries. Chronic urticaria has a high impact on the quality of life and daily activities of patients. Therefore, if causal factors cannot be eliminated, effective symptomatic treatment is necessary. The recommended first-line treatment is to administer new generation, non-sedating H1 antihistamines. If the standard dose is not sufficiently effective, the dose should be increased up to fourfold. For patients who do not respond to this treatment, the second-line treatment in addition to antihistamines in the treatment algorithm is omalizumab and, if this treatment fails, ciclosporin. Other low-evidence therapeutic agents should only be used if all treatments in the treatment algorithm agreed upon by the guideline group fail. Both the benefit-risk profile and cost should be considered. Corticosteroids are not recommended for long-term treatment due to their inevitable severe side effects.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Qualidade de Vida , Doença Crônica , Urticária/tratamento farmacológico , Urticária Crônica/diagnóstico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêuticoRESUMO
Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.
Assuntos
Antialérgicos , Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Antialérgicos/uso terapêutico , Doença Crônica , Urticária Crônica Induzida , Urticária Crônica/tratamento farmacológico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Omalizumab/uso terapêutico , Urticária/diagnóstico , Urticária/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Literature on the effects of second-generation H1-antihistamines on angiogenesis is limited. OBJECTIVES: To investigate the effects of cetirizine, desloratadine, and rupatadine (second-generation H1-antihistamines commonly used in dermatology clinics) on angiogenesis in an in vivo chick chorioallantoic membrane (CAM) model. METHODS: The study was approved by the local ethics committee on animal experimentation. Forty fertilized specific pathogen free eggs were incubated and kept under appropriate temperature and humidity control. Drug solutions were prepared in identical concentrations by dissolving powders in phosphate-buffered saline (PBS). On the third day of the incubation, a small window was opened on the CAM and 0.1 mL desloratadine (1.5 µg/0.1 mL) in the first group, 0.1 mL cetirizine (1.5 µg/0.1 mL) in the second group, 0.1 mL rupatadine in the third group (1.5 µg/0.1 mL), and PBS (0.1 mL) in the fourth group were administered by injection. On the eighth day of incubation, the vascular structures of the CAMs were macroscopically examined and standard digital photographs were taken. The digital images were analyzed and data including mean vessel density, thickness, and number were compared between groups. p < 0.05 was considered statistically significant. RESULTS: Vessel densities were similar in the desloratadine, cetirizine, and control groups, whereas they were significantly less in the rupatadine group (p = 0.01). Furthermore, the rupatadine group had significantly lower vessel thickness and number compared with the other groups (p < 0.05 for both). CONCLUSIONS: Rupatadine showed anti-angiogenic effects in the chick CAM model, compared with desloratadine and cetirizine. The anti-angiogenic effect of rupatadine could be due to its platelet-activating factor (PAF) receptor inhibition. Thus, rupatadine could be a treatment agent in pathological processes in which angiogenesis is responsible. Further studies with larger series are needed to clarify this potential.
Assuntos
Cetirizina , Antagonistas não Sedativos dos Receptores H1 da Histamina , Animais , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Membrana Corioalantoide , GalinhasRESUMO
Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.
Assuntos
Urticária Crônica , Antagonistas não Sedativos dos Receptores H1 da Histamina , Urticária , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Portugal/epidemiologia , Estudos Retrospectivos , Diagnóstico Tardio , Urticária/diagnóstico , Urticária/tratamento farmacológico , Urticária/epidemiologia , Urticária Crônica/tratamento farmacológico , Omalizumab/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Urticária Crônica Induzida , Doença CrônicaRESUMO
BACKGROUND: Guidelines recommend standard doses of antihistamines as first-line, and updosing of antihistamines as second-line treatment for the management of chronic urticaria (CU). However, remission rates with different types of first- and second-line treatments and indicators of antihistamine response are largely lacking in the literature. OBJECTIVES: To examine response rates to first- and second-line treatments in CU, and to identify patient characteristics that can predict antihistamine treatment outcomes. METHODS: We retrospectively analyzed treatment outcomes of 657 CU (556 chronic spontaneous urticaria (CSU), 101 chronic inducible urticaria (CIndU)) patients who had at least 3-months of follow-up data. RESULTS: A standard dose of second generation antihistamines (sgAH) was effective in 43.1 % of the patients. An additional 28.8 % of patients were in remission with second-line treatments. Among patients whose disease was in remission with a standard dose of sgAHs, 14.8 % benefited from switching from their current sgAH to another sgAH. Updosing sgAHs, combination of two different sgAHs, sgAH and first generation H1-antihistamine combination, and sgAH and leukotriene receptor antagonist combination provided remission in 38.3 %, 35.8 %, 37.5 % and 25 % of patients who were given these treatments, respectively. Baseline UCT score ≤ 4, emergency referral and family history of CSU were found to be risk factors for antihistamine refractoriness in patients with CSU. CONCLUSIONS: A step-wise approach to the management of CU is practical as more patients respond to treatment at each step. The presence of baseline UCT score ≤ 4, emergency referral and family history of CSU might be helpful to determine patients who require third-line treatments in advance.