Effect of Loratadine for Pegfilgrastim-Induced Bone Pain.

AIMS: Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment recommendations include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and/or antihistamine use. However, little research was found comparing these interventions. The study aim was to address the gaps in literature and to explore the use of and perceived effectiveness of loratadine versus acetaminophen or NSAIDs in women with breast cancer treated with pegfilgrastim. This study also sought to understand how patients became aware of loratadine or other treatments for management of bone pain. DESIGN/METHODS: This cross-sectional study used survey methods to collect data from 66 adult female breast cancer patients receiving chemotherapy with pegfilgrastim. RESULTS: The incidence of bone pain was 45% (n = 30) in our sample, but more than half (n = 45; 69%) of the women took either acetaminophen, NSAIDs, or loratadine alone or in combination to prevent bone pain. All medication were rated as effective by patients, with acetaminophen slightly more effective than loratadine, and loratadine more effective than NSAIDs. CONCLUSIONS: Acetaminophen, NSAIDs, and loratadine are easily available and inexpensive. However, unlike acetaminophen and NSAIDs, loratadine is dosed once a day and well tolerated with minimal adverse effects. CLINICAL IMPLICATIONS: Randomized controlled trials are needed to adequately assess the effectiveness of all three medication options. Because little is known about optimal use of any of these medications for pegfilgrastim-induced bone pain, it is also important to identify the optimal time to initiate treatment and ideal treatment duration.

Effect of Loratadine Tablets in Combination with Other Drugs on Nasal Physiological Function and T Lymphocyte Subsets in Patients with Allergic Rhinitis.

Objective: To investigate the effects of loratadine tablets in combination with other drugs on nasal physiological function and T lymphocyte subsets in patients with allergic rhinitis (AR). Methods: A total of 120 AR patients treated in our hospital from February 2018 to February 2021 were randomly divided into control group and research group. The control group was given mometasone furoate nasal spray combined with loratadine tablets, while the research group was given budesonide combined with loratadine. The efficacy, duration of clinical symptom remission, immune function indicators, T lymphocyte subset, nasal physiological function, and incidence of adverse reactions were compared between the two groups. Results: The efficacy results of the two groups showed that the effective rate of the research group was 96.67%, while the effective rate of the control group was 83.33%. The effective rate in the research group was higher compared to the control group (χ 2: 5.925 P < 0.05). The results of clinical symptom relief time showed that the clinical symptom relief time of nasal congestion, itching, runny nose, and sneezing in the research group was lower than that in the control group, and the difference was statistically significant (P < 0.05). The results of the comparison of immune function indicators showed that the IL-6, IL-8, and IgE of the research group were lower than those of the control group, while the Th1/Th2 of the research group were higher than those of the control group. There were no statistically significant differences in T lymphocyte subsets before nursing, but after treatment, the T lymphocyte subsets of the two groups decreased, and the level of CD3+, CD4+, CD8+, CD4+, and CD4+/CD8+ lymphocytes in the research group was lower than that of the control group, and the difference was statistically significant (P < 0.05). Before treatment, there exhibited no significant difference in nasal physiological function, but after treatment, the nasal physiological function of the two groups was enhanced, and the MTT, NR, and MCR of the research group were lower than those of the control group, and the difference was statistically significant (P < 0.05). Finally, the incidence of adverse reactions in the research group was lower compared to the control group, and the difference was statistically significant (P < 0.05). Conclusion: Budesonide and loratadine are effective in improving patient efficacy, T lymphocyte subsets, and nasal physiological function, and are safer.

Evaluation of efficiency and safety of combined loratadine and budesonide in patients with anaphylactic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Among the most prevalent allergic conditions that affect children is anaphylactic rhinitis (AR). It is capable of leading to physical as well as mental health issues. Concomitant use of loratadine and budesonide may improve symptoms of AR more than treatment with either drug alone. To assess the efficacy and safety of combined loratadine and budesonide for patients experiencing AR is the aim of this study. METHODS: We will apply 2 independent authors in six databases, including EMBASE, Pub Med, Web of Science, China National Knowledge Infrastructure, WanFang Database, Chinese Scientific Journal Database (VIP database). Studies evaluating the efficacy and safety of combined loratadine and budesonide in patients with AR will include studies published between inception and Dec 2021. Accordingly, the data will have to be in English and Chinese. For the selection of data extraction, the studies and risk of bias assessment will be completed by 2 independent authors. Accordingly, data synthesis will be conducted through RevMan 5.3 software. The study will establish heterogeneity using the I2 test. Without correct data or information, there is a need for Publication bias, which is assessed by performing the Begg and Egger test and generating a funnel plot. RESULTS: The study provides a trustable clinical foundation for loratadine and budesonide for AR treatment.OSF registration number: DOI 10.17605/OSF.IO/M2RFGEthics and dissemination: Because the present study is founded on existing studies, it does not require ethics approval.

Comparative nasal airflow with loratadine-pseudoephedrine and fluticasone nasal spray for allergic rhinitis.

BACKGROUND: Although it is known that oral antihistamine-pseudoephedrine combination tablets have a faster onset than intranasal corticosteroid sprays in the treatment of allergic rhinitis after the first dose, the magnitude of change has not been measured in a comparative manner. Furthermore, the sensation of sprayed liquid in the nose may lead patients to mistakenly believe that intranasal steroid sprays work instantly. OBJECTIVE: To evaluate, numerically, nasal airflow changes provided by a single dose of loratadine-pseudoephedrine tablet (LP) and fluticasone propionate nasal spray (FP) in participants experiencing allergic rhinitis symptoms, including nasal congestion. METHODS: This single-center, double-blinded, placebo-controlled, crossover study evaluated objective nasal airflow changes in patients with a documented sensitivity to ragweed pollen. Participants were randomized to receive 1 of 4 treatment sequences, and their peak nasal inspiratory flow (PNIF) was measured in a span of 4 hours after pollen exposure in an environmental exposure unit. RESULTS: Average change in PNIF was 31% with LP in the course of the study, significantly greater than with placebo and FP (12% and 15%, respectively; P < .001). Nevertheless, FP did not produce a significant change compared with its placebo. At hour one post-dose, LP had a clinically significant 31% increase in PNIF, whereas FP only yielded an 8.6% increase (P < .001). Measurable nasal airflow improvements are associated with the opening of nasal passages, allowing congested patients to breathe more freely. CONCLUSION: A single dose of LP quickly and significantly (P < .001) improved nasal airflow after ragweed pollen challenge in an environmental exposure unit. Comparatively, FP did not display this same benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03443843.

The risk of fractures, acute myocardial infarction, atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine.

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07-2.63 and OR 3.22; 95% CI 1.69-7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94-5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.

Human H1 receptor (HRH1) gene polymorphism is associated with the severity of side effects after desloratadine treatment in Chinese patients with chronic spontaneous uticaria.

H1 nonsedating antihistamines, such as desloratadine, are first-line treatment options for chronic spontaneous urticaria (CSU). However, desloratadine induces various degrees of sedation side effect in CSU patients, and no biomarkers currently exist for predicting the severity of such side effect. Herein, we evaluated the association between HRH1 gene rs901865 polymorphism and the severity of sedation side effect following desloratadine therapy in patients with CSU. We found that 20 of the 114 patients (17.50%) showed sedation side effect after desloratadine treatment, and 3 patients (2.63%) experienced serious sleepiness. The frequency of HRH1 rs901865 G allele was significantly higher in patients who experienced sedation than in patients with rs901865 A allele (p = 0.0009). Moreover, patients with the rs901865 G/G genotype suffered a more serious sedation side effect than patients with the rs901865 G/A genotype (p = 0.005). These results provide evidence that the HRH1 rs901865 G/G polymorphism is associated with severe sedation side effect after desloratadine treatment. Thus, the HRH1 rs901865 allele may potentially be used as a biomarker for predicting the severity of sedation side effect in patients suffering from CSU and treated with desloratadine.

Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study.

BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.

Oral H1 antihistamines as 'add-on' therapy to topical treatment for eczema.

BACKGROUND: The symptoms of eczema can lead to sleeplessness and fatigue and may have a substantial impact on quality of life. Use of oral H1 antihistamines (H1 AH) as adjuvant therapy alongside topical agents is based on the idea that combining the anti-inflammatory effects of topical treatments with the blocking action of histamine on its receptors in the skin by H1 AH (to reduce the principal symptom of itch) might magnify or intensify the effect of treatment. Also, it would be unethical to compare oral H1 AH alone versus no treatment, as topical treatment is the standard management for this condition. OBJECTIVES: To assess the effects of oral H1 antihistamines as 'add-on' therapy to topical treatment in adults and children with eczema. SEARCH METHODS: We searched the following databases up to May 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and the GREAT database (Global Resource of EczemA Trials; from inception). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We also searched the abstracts of four conference proceedings held between 2000 and 2018. SELECTION CRITERIA: We sought RCTs assessing oral H1 AH as 'add-on' therapy to topical treatment for people with eczema compared with topical treatment plus placebo or no additional treatment as add-on therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcome measures were 'Mean change in patient-assessed symptoms of eczema' and 'Proportion of participants reporting adverse effects and serious adverse events'. Secondary outcomes were 'Mean change in physician-assessed clinical signs', 'Mean change in quality of life', and 'Number of eczema flares'. MAIN RESULTS: We included 25 studies (3285 randomised participants). Seventeen studies included 1344 adults, and eight studies included 1941 children. Most studies failed to report eczema severity at baseline, but they were conducted in secondary care settings, so it is likely that they recruited patients with more severe cases of eczema. Trial duration was between three days and 18 months. Researchers studied 13 different H1 AH treatments. We could not undertake pooling because of the high level of diversity across studies in terms of duration and dose of intervention, concomitant topical therapy, and outcome assessment. Risk of bias was generally unclear, but five studies had high risk of bias in one domain (attrition, selection, or reporting bias). Only one study measured quality of life, but these results were insufficient for statistical analysis.Although this review assessed 17 comparisons, we summarise here the results of three key comparisons in this review.Cetirizine versus placeboOne study compared cetirizine 0.5 mg/kg/d against placebo over 18 months in 795 children. Study authors did not report patient-assessed symptoms of eczema separately for pruritus. Cetirizine is probably associated with fewer adverse events (mainly mild) (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.46 to 1.01) and the need for slightly less additional H1 AH use as an indication of eczema flare rate (P = 0.035; no further numerical data given). Physician-assessed clinical signs (SCORing Atopic Dermatitis index (SCORAD)) were reduced in both groups, but the difference between groups was reported as non-significant (no P value given). Evidence for this comparison was of moderate quality.One study assessed cetirizine 10 mg/d against placebo over four weeks in 84 adults. Results show no evidence of differences between groups in patient-assessed symptoms of eczema (pruritus measured as part of SCORAD; no numerical data given), numbers of adverse events (RR 1.11, 95% CI 0.50 to 2.45; mainly sedation, other skin-related problems, respiratory symptoms, or headache), or physician-assessed changes in clinical signs, amount of local rescue therapy required, or number of applications as an indicator of eczema flares (no numerical data reported). Evidence for this comparison was of low quality.Fexofenadine versus placeboCompared with placebo, fexofenadine 120 mg/d taken in adults over one week (one study) probably leads to a small reduction in patient-assessed symptoms of pruritus on a scale of 0 to 8 (mean difference (MD) -0.25, 95% CI -0.43 to -0.07; n = 400) and a greater reduction in the ratio of physician-assessed pruritus area to whole body surface area (P = 0.007; no further numerical data given); however, these reductions may not be clinically meaningful. Results suggest probably little or no difference in adverse events (mostly somnolence and headache) (RR 1.05, 95% CI 0.74 to 1.50; n = 411) nor in the amount of 0.1% hydrocortisone butyrate used (co-intervention in both groups) as an indicator of eczema flare, but no numerical data were given. Evidence for this comparison was of moderate quality.Loratadine versus placeboA study of 28 adults compared loratadine 10 mg/d taken over 4 weeks versus placebo. Researchers found no evidence of differences between groups in patient-assessed pruritus, measured by a 100-point visual analogue scale (MD -2.30, 95% CI -20.27 to 15.67); reduction in physician-assessed clinical signs (SCORAD) (MD -4.10, 95% CI -13.22 to 5.02); or adverse events. Study authors reported only one side effect (folliculitis with placebo) (RR 0.25, 95% CI 0.01 to 5.76). Evidence for this comparison was of low quality. Number of eczema flares was not measured for this comparison. AUTHORS' CONCLUSIONS: Based on the main comparisons, we did not find consistent evidence that H1 AH treatments are effective as 'add-on' therapy for eczema when compared to placebo; evidence for this comparison was of low and moderate quality. However, fexofenadine probably leads to a small improvement in patient-assessed pruritus, with probably no significant difference in the amount of treatment used to prevent eczema flares. Cetirizine was no better than placebo in terms of physician-assessed clinical signs nor patient-assessed symptoms, and we found no evidence that loratadine was more beneficial than placebo, although all interventions seem safe.The quality of evidence was limited because of poor study design and imprecise results. Future researchers should clearly define the condition (course and severity) and clearly report their methods, especially participant selection and randomisation; baseline characteristics; and outcomes (based on the Harmonising Outcome Measures in Eczema initiative).

Desloratadine and depression, a drug safety signal based on worldwide spontaneous reporting of side effects.

OBJECTIVE: Desloratadine, a third-generation antihistamine, is claimed to cause fewer central nervous system (CNS) adverse drug reactions (ADRs) than antihistamines of the first- and second-generation. While literature is inconclusive regarding the possible CNS effects, symptoms like somnolence and hallucinations are acknowledged ADRs of desloratadine, indeed suggesting some passage of this drug across the blood-brain barrier. Depression is currently not described as an ADR in the approved desloratadine product labelling. MATERIALS AND METHODS: In a joint signal detection workshop with the Uppsala Monitoring Centre and the Netherlands Pharmacovigilance Centre Lareb, case reports of suspected drug-ADR associations were analysed. RESULTS: Forty-nine unique case reports of desloratadine associated with depression or depressed mood were detected in the WHO global ADR database. In these reports, the median time to onset of depression was three days. Most patients recovered after withdrawal of desloratadine, and in five patients the symptoms of depression recurred after re-administration of desloratadine. CONCLUSION: We hypothesize that desloratadine may enter the CNS and that it hence in rare cases may cause a clinically relevant state of depression, a relation that patients and their treating physicians should be made aware of.

Posible relación de loratadina con el desenlace fatal en un paciente de riesgo / Possible link of loratadine with a fatal outcome in an at-risk patient

Un varón de 62 años, polimedicado de forma crónica por enfermedad mental grave y persistente, EPOC, diabetes e hipotiroidismo, estabilizado desde hace bastantes meses, inició un tratamiento con loratadina por rinitis. Al día siguiente es encontrado desvanecido sin conocimiento y trasladado de urgencia al hospital general para cuidados intensivos, donde fallece un día después. El análisis del caso revela un posible «efecto mariposa» con desenlace fatal, desencadenado por un fármaco de bajo riesgo, dada la situación «al límite» de la terapia previa (AU)

A 69-year-old man, who has been clinically chronic for severe and persistent mental illness, COPD, diabetes and hypothyroidism, stabilized for several months, began treatment with loratadine for rhinitis. The next day he is found unconscious and rushed to the general hospital for intensive care, where he dies a day later. The case analysis reveals a possible «butterfly effect», a fatal outcome caused by a low risk drug, given the «borderline» situation of prior therapy (AU)

The treatment outcomes and dose de-escalation of desloratadine up-dosing in chronic spontaneous urticaria.

BACKGROUND: An increase in dosages up to fourfold of second generation antihistamines is recommended for recalcitrant chronic spontaneous urticaria (CSU). No regimen guidelines about dose de-escalation, however, are mentioned once the disease is controlled. OBJECTIVE: To demonstrate the treatment outcomes and dose reduction in desloratadine assessed using the urticarial activity score over 7 consecutive days. METHODS: Medical records of all patients with CSU treated with desloratadine were collected retrospectively during a period from January 2010 to December 2013. RESULTS: Sixty-seven (94.4%) patients had remission of the disease with variable doses of desloratadine. The patients who had CSU concomitant with antithyroid antibodies or high erythrocyte sedimentation rates had a greater tendency not to respond to the standard dose. Once the disease was completely controlled, 67 patients finished the treatment, but 63 (94%) patients had recurrent symptoms. Sixty-three patients took the same dose that induced the response for a further 4 weeks before stopping or reducing the dose, 41/63 (65.1%), however developed urticaria again. Forty-one patients took the same dose for a further 8 weeks; only 2/41 (4.9%) patients developed the rash again. The mean follow-up period after the disease was controlled was 7.5 months. CONCLUSION: Most patients need higher than the standard doses to obtain remission. Once the disease is completely controlled, however, maintenance of the same dosage for at least 8 weeks before dose reduction is suggested in order to avoid recurrence of the symptoms.

ATR-FTIR spectroscopy and µ-EDXRF spectrometry monitoring of enamel erosion caused by medicaments used in the treatment of respiratory diseases.

Medicaments essential for alleviation of diseases may sometime adversely affect dental health by eroding the enamel, owing to their acidic nature. It is therefore highly desirable to be able to detect these effects quickly and reliably. In this study, we evaluated the erosive capacity of four most commonly prescribed respiratory disease syrup medicaments on enamel using micro-energy-dispersive X-ray fluorescence spectrometry (µ-EDXRF) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Fifty-five enamel fragments obtained from 30 bovine teeth were treated with artificial saliva (S), acebrofilin hydrochloride (AC), ambroxol hydrochloride (AM), bromhexine hydrochloride (BR), and salbutamol sulfate (SS); by immersing in 3 mL of respective solutions for 1 min, three times a day at intervals of 1 hr, for 5 days. µ-EDXRF analysis of enamel surface did not reveal significant erosion caused by the medications. However, ATR-FTIR showed a detectable shift in the phosphate (PO4 ) antisymmetric stretching mode (ν3 ) at ∼985 cm-1 for AM, BR, and SS, indicating erosion. Multivariate statistical analysis showed that AC, AM, SS, and BR could be classified with 70%, 80%, 100%, and 100% efficiency from S (control), further highlighting the ability of ATR-FTIR to identify degree of erosion. This suggests ATR-FTIR may be used to rapidly and nondestructively investigate erosive effects of medicaments.

Drug interaction at hERG channel: In vitro assessment of the electrophysiological consequences of drug combinations and comparison against theoretical models.

Drugs carry a proarrhythmic risk, which gets even greater when they are used in combination. In vitro assessment of the proarrhythmic potential of drugs is limited to one compound and thus neglects the potential of drug-drug interactions, including those involving active metabolites. Here we present the results of an in vitro study of potential drug-drug interactions at the level of the hERG channel for the combination of up to three compounds: loratadine, desloratadine and ketoconazole. Experiments were performed at room temperature on an automated patch-clamp device CytoPatch 2, with the use of heterogeneously, stably transfected HEK cells. Single drugs, pairs and triplets were used. The results provided as the inhibition of the IKr current for pairs were compared against the calculated theoretical interaction. Models applied to calculate the combined effect of inhibitory actions of simultaneously given drugs include: (1) simple additive model with a maximal inhibition limit of 1 (all channels blocked in 100%); (2) Bliss independence; and (3) Loewe additivity. The observed IC50 values for loratadine, desloratadine and ketoconazole were 5.15, 1.95 and 0.74 µm respectively. For the combination of drugs tested in pairs, the effect was concentration dependent. In lower concentrations, the synergistic effect was observed, while for the highest tested concentrations it was subadditive. To triple the effect, it was subadditive regardless of concentrations. The square root of sum of squares of differences between the observed and predicted total inhibition was calculated to assess the theoretical interaction models. For most of the drugs, the allotopic model offered the best fit.

Association between desloratadine and prednisolone in the treatment of children with acute symptoms of allergic rhinitis: a double-blind, randomized and controlled clinical trial / Associação entre desloratadina e prednisolona no tratamento de crianças com sintomas agudos de rinite alérgica: ensaio clínico duplo-cego, randomizado e controlado

Abstract Introduction: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. Objective: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years) with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. Methods: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12] ≥ 6) were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n = 105; three daily doses) or desloratadine plus prednisolone (n = 105; single dose followed by two of placebo) for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. Results: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14% × 8.57%, respectively). Conclusion: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the dexchlorpheniramine plus betamethasone combination, it showed similar clinical action, but with a lower incidence of adverse events and higher dosing convenience.

Resumo Introdução: A associação entre anti-histamínicos e corticosteroides orais é frequentemente empregada no tratamento de sintomas agudos de rinite alérgica. Objetivo: Avaliar a segurança e eficácia da associação desloratadina + prednisolona no tratamento de sintomas agudos de crianças (2-12 anos) com rinite alérgica e compará-las com as da associação dexclorfeniramina + betametasona. Método: Crianças com rinite alérgica persistente moderada/grave e sintomáticas (escore de sintomas nasais [0-12] ≥ 6) foram alocadas de modo duplo-cego e randômico para receber dexclorfeniramina + betametasona (n = 105; três doses diárias) ou desloratadina + prednisolona (n = 105; dose única seguida por duas de placebo) por 7 dias. No início e no fim da avaliação foram obtidos: escore de sintomas nasais, escore de sintomas extranasais, pico de fluxo inspiratório nasal, bioquímica sanguínea e eletrocardiograma. Do total, 96 crianças do grupo dexclorfeniramina + betametasona e 98 do grupo desloratadina + prednisolona concluíram o protocolo. Resultados: Os dois grupos foram iguais com relação ao escore de sintomas nasais, escore de sintomas nasais extranasais e pico de fluxo inspiratório nasal iniciais e finais. Observou-se queda de 76,4% e 79,1% nos escores para escore de sintomas nasais, de 86,0% e 79,2% para escore de sintomas extranasais, assim como incremento de 25,2% e de 24,3% para o pico de fluxo inspiratório nasal para os grupos desloratadina + prednisolona e dexclorfeniramina + betametasona, respectivamente. Não houve alterações significativas da bioquímica sanguínea. Taquicardia sinusal foi a alteração do eletrocardiograma mais encontrada, mas sem significância clínica. Sonolência foi significantemente mais referida entre os tratados com dexclorfeniramina + betametasona do que entre os desloratadina + prednisolona (8,57% × 17,14%, respectivamente). Conclusão: A associação desloratadina + prednisolona foi capaz de controlar efetivamente os sintomas agudos de rinite em crianças, melhorou sintomas e a função nasal. Na comparação com a associação dexclorfeniramina + betametasona, demonstrou ação clínica semelhante, mas com menor incidência de eventos adversos e maior comodidade posológica.

Safety profile of H1-antihistamines in pediatrics: an analysis based on data from VigiBase.

PURPOSE: H1-antihistamines are commonly used in infants and children for the relief of histamine-mediated symptoms in a variety of conditions. Little is known about their safety profile in these patients. We performed a comparative analysis of the safety profiles of H1-antihistamines using data from the WHO database (VigiBase). METHODS: We selected adverse drug reaction (ADR) reports on H1-antihistamines in children (0-16 years) up to June 2014 from VigiBase. ADRs were codified according to MedDRA terminology. The reporting odds ratios (RORs) with 95% confidence for drug-reaction pairs were calculated. RESULTS: The analysis was performed on 8918 reports related to antihistamines, corresponding to 19503 drug reaction pairs for 68 different drugs. Most of reports involved children aged 2 to 6 years (32%) and 6 to 12 years (34%). Most reported drugs were cetirizine (1608 reports, corresponding to 18%), loratadine (16%), and diphenhydramine (10%). ADRs were classified as serious in 23% of cases, and 400 cases had a fatal outcome. We found a significant associations for several drug-reaction pairs such as levocetirizine and epilepsy (ROR, 6.57; 95% confidence interval [CI], 1.51-28.53) and chlorphenamine and toxic epidermal necrolysis (ROR, 7.29; 95% CI, 2.39-22.2). CONCLUSIONS: H1-antihistamines are among the most used drugs in pediatrics, also in an off-label manner. Our data highlights associations with serious and unexpected ADRs. Educative intervention to clinicians and parents are needed to help doctors to make proper choices on the drug treatment and for the early detection of ADRs to maximize the benefits and reduce the risk of ADRs in these patients.

Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis.

BACKGROUND: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children. OBJECTIVE: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup in a randomized double-blind study of children, ages 6-11 years, with SAR. METHODS: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n = 231) for 2 weeks. The primary efficacy end point was change from baseline in the subject's mean reflective total symptom severity complex (TSSC) score over 14 days. RESULTS: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated with placebo over 14 days (least square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score improvement over 14 days between the cetirizine versus loratadine groups (-2.1 versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8 versus -1.6; p = 0.230) were not statistically significant. Predominant adverse events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects. CONCLUSION: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR symptoms in children ages 6-11 years. Symptom improvement was not significantly different between the loratadine 10 mg and placebo groups.

Association between desloratadine and prednisolone in the treatment of children with acute symptoms of allergic rhinitis: a double-blind, randomized and controlled clinical trial.

INTRODUCTION: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. OBJECTIVE: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years) with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. METHODS: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12]≥6) were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n=105; three daily doses) or desloratadine plus prednisolone (n=105; single dose followed by two of placebo) for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. RESULTS: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14%×8.57%, respectively). CONCLUSION: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the dexchlorpheniramine plus betamethasone combination, it showed similar clinical action, but with a lower incidence of adverse events and higher dosing convenience.

Efficacy and safety of using a warming needle for persistent allergic rhinitis: study protocol for a randomized controlled trial.

BACKGROUND: Many previous studies have shown the potential therapeutic effect of acupuncture for allergic rhinitis. Most of these studies, however, were limited by the short duration of observations and lack of sham acupuncture as the control group. Our preliminary experiments showed that the use of a warm needling achieved a much more persistent effect in the treatment of allergic rhinitis (AR) compared with simple acupuncture therapy. Hence, we have designed a multicenter, randomized controlled trial (RCT) in which the first-line medication loratadine will be used as the control group, and the effect of warm needling therapy will be evaluated through long-term observation. METHODS/DESIGN: The trial is designed as a multicenter, parallel-group, randomized, single-blinded (outcome assessors), non-inferiority trial. A total of 98 patients with persistent AR will be randomly assigned into two groups. Patients in the treatment group will be treated with warm needling at GV14 and acupuncture at EX-HN3, ST2, LI20, EX-HN8, GV23, LU7, LU5 and LI4 three times a week, for a total of 4 weeks. Patients in the control group will be treated with oral loratadine 10 mg/day for 4 weeks. The primary outcome will be the change in the Total Nasal Symptom Score (TNSS) from baseline to that at 6 months after treatment during the follow-up period. The secondary outcomes will include the Total Non-nasal Symptom Score and the Rhinoconjunctivitis Quality of Life Questionnaire, changes in the TNSS from baseline to that at 2 and 4 weeks during treatment, and 3 months after treatment during the follow-up period. Outcomes will be measured at 2 and 4 weeks, and 3 and 6 months after treatment. Any side effects of treatment will be observed and recorded. DISCUSSION: We expect that the study results will provide evidence to determine the effects of warm needling compared with loratadine. Our final goal of the study is to evaluate the difference in the short-term and long-term effects between the two therapeutic methods, especially the long-term effect of warm needling. TRIAL REGISTRATION: ClinicalTrials.gov NCT02339714 . Registered on 14 January 2015.

Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years.

BACKGROUND: Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. METHODS: A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2-11 years with CSU, with or without angio-oedema. Patients received either rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. RESULTS: The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (-5.5 ± 7.5 placebo, -11.8 ± 8.7 rupatadine and -10.6 ± 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for rupatadine followed by desloratadine (-48.4%) and placebo (-30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (-57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. CONCLUSION: Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (ß) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.