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.

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.

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).

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.

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.

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.

Maternal exposures in the National Birth Defects Prevention Study: Time trends of selected exposures.

BACKGROUND: Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). METHODS: We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 to 2011. Mothers from the 10 participating centers across the United States were interviewed by phone between 6 weeks and 2 years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors, and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall's τß test statistic. RESULTS: The exposure trend analysis included 11,724 control mothers with EDDs from 1998 to 2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of selective serotonin reuptake inhibitors and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. CONCLUSION: Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures.

[Fixed pigmented erythema antihistamine H1: about 2 cases and review of the literature]. / Érythème pigmenté fixe aux antihistaminiques H1 : à propos de 2 cas et revue de la littérature.

We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case).

The effect of antiallergic treatment with desloratadine-montelukast on salivary glands function in allergic rhinitis.

The aim of this study was to evaluate the possible favorable effect of desloratadine-montelukast combination on salivary glands (SG) function in patients with allergic rhinitis (AR) using SG scintigraphy. The study population consisted of 64 patients with AR and 28 healthy controls: 14 males and 14 females, with mean age 32.3±8.6 years. The patients were divided into two groups: the untreated patients group of 32 patients, 16 males and 16 females, mean age 28.5±5.4 years and the treated group, who received the standard clinically recommended oral dose of montelukast 10mg/d and desloratadine 5mg/d for 6 weeks. This group consisted of 32 patients, 16 males and 16 females, mean age 38.3±8.4 years. All patients and healthy controls underwent SG scintigraphy. After the intravenous injection of technetium-99m pertechnetate, ((99m)Tc-P), dynamic SG scintigraphy was performed for 25min. Using the time-activity curves, the following glandular function parameters were calculated for the parotid and the submandibular SG: uptake ratio, maximum accumulation and ejection fraction. Results showed SG hypofunction. All functional parameters obtained for the untreated patients and for the desloratadine-montelukast treated patients were significantly lower than those in healthy controls (P<0.05). There was no statistically significant difference between treated and untreated patients (P>0.05). In conclusion, our study showed that hypofunction of SG was present in all patients with AR. This hypofunction, as tested by semi-quantitative SG scintigraphy, and also the quality of life did not improve after treatment with montelukast and desloratadine.

Oral isotretinoin with desloratadine compared with oral isotretinoin alone in the treatment of moderate to severe acne: a randomized, assessor-blinded study.

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.

Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions.

Drug-drug interactions (DDIs) are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP) metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR = 1.69); loratadine and alprazolam (RR = 1.86); loratadine and duloxetine (RR = 1.94); loratadine and ropinirole (RR = 3.21); and promethazine and tegaserod (RR = 3.00). When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms.

Seizures induced by desloratadine, a second-generation antihistamine: clinical observations.

Some clinical experiences indicate that H1-antihistamines, especially first-generation H1-antagonists, occasionally provoke convulsions in healthy children as well as epileptic patients. Desloratadine is a frequently used second-generation antihistamine considered to be effective and safe for the treatment of allergic diseases. We describe four children who experienced epilepsy associated with the nonsedating H(1)-antagonist desloratadine and discuss the neurophysiologic role of the central histaminergic system in seizure susceptibility. In conclusion, we recommend caution in treating epileptic patients with the histamine H(1)-antagonists, including second- and third-generation drugs that are frequently referred because they are considered to be nonsedating antihistamines.

Can on-demand non-sedating antihistamines improve urticaria symptoms? A double-blind, randomized, single-dose study.

Non-sedating H1-antihistamines are the recommended first-line treatment for chronic spontaneous urticaria. While efficacy studies usually apply continuous daily treatment regimens, many patients take their medication on demand. In this randomized, double-blind trial we tested whether on-demand H1-antihistamine desloratadine in standard and higher doses is able to improve the resolution of existing wheals. Symptoms of 29 patients with chronic spontaneous urticaria were followed without treatment on one day and again on another day during the next 3 weeks after a single dose of either 5 mg or 20 mg desloratadine, using different objective measures. While the intervention with both doses of desloratadine was effective in terms of a reduction in hyperthermic skin area, there was no improvement in wheal area and wheal volume compared with no treatment. Wheal numbers were reduced after treatment with 20 mg, but not 5 mg, desloratadine. In conclusion, the beneficial effects of non-sedating H1-anti-histamines given on demand appear to be low. Thus, a preventive treatment strategy should be preferred in chronic spontaneous urticaria.

Critical temperature threshold measurement for cold urticaria: a randomized controlled trial of H(1) -antihistamine dose escalation.

BACKGROUND: Cold urticaria is a rare but severe and potentially lethal condition. It is primarily treated symptomatically with H(1) -antihistamines. However, patients have a variable response to these drugs and, to date, it has not been possible to predict readily the response to therapy of individual patients. OBJECTIVES: To assess the severity of the cold urticaria in naive patients and the response to therapy of patients treated with increasing doses of an H(1) -antihistamine by measurement of critical temperature thresholds (CTT) for producing weals on the forearm. METHODS: This was a two-centre, hospital-based, double-blind, randomized, parallel-group study of patients with a confirmed diagnosis of cold urticaria of at least 6 months' duration. Patient groups received either a constant dose of desloratadine 5 mg daily for 6 weeks (n = 13), or escalating doses of desloratadine: 5 mg daily for the first 2 weeks, 10 mg daily for the second 2 weeks and 20 mg daily for the final 2 weeks (n = 15). Only one adverse event that appeared to be drug related was reported: mild fatigue after treatment with desloratadine 10 mg that lasted for about 3 weeks and resolved at the end of the study. RESULTS: The desloratadine 5 mg daily dose produced a submaximal reduction of mean CTT which remained relatively constant over 6 weeks. Dose escalation increased efficacy, the reduction in mean CTT at four-times the standard daily dose being significantly greater (P = 0·03) than with the standard dose. Individually, no patient became symptom free (CTT < 4 °C) on 5 mg, while two became symptom free on 10 mg and a further three on 20 mg desloratadine daily. CONCLUSIONS: Measurement of CTT allows for individualized risk management and therapy in patients with cold urticaria.

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.

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.

NSAID-sensitive antihistamine-induced urticaria/angioedema.

We present a case of urticaria caused by antihistamines in a patient with nonsteroidal anti-inflammatory drug (NSAID) sensitivity. A 35-year-old man experienced, on 2 separate occasions, immediate generalized urticaria during treatment with ibuprofen and naproxen, respectively. A single-blind, placebo-controlled oral challenge (SBPCOC) with piroxicam was carried out, and resulted in urticaria and angioedema 3 hours later. Two hours after initial clinical resolution, the patient developed multiple wheals on the trunk and upper limbs. He described similar delayed reactions after oral antihistamine administration on previous occasions. SBPCOCs with acetaminophen and etoricoxib were performed, with good tolerance. Skin prick and patch tests with loratadine and cetirizine were negative. After an SBPCOC with loratadine, the patient developed generalized urticaria 90 minutes after intake. Tolerance to fexofenadine 180 mg was confirmed. We describe the first case of a possible new subset of antihistamine urticaria, and suggest calling this NSAID-sensitive antihistamine-induced urticaria/angioedema.