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Two accurate, precise and robust multivariate chemometric methods were developed for the simultaneous determination of montelukast sodium (MON), rupatadine fumarate (RUP) and desloratadine (DES). These methods provide a cost-effective alternative to chromatographic techniques by utilizing spectrophotometry in pharmaceutical quality control. The proposed approaches, partial least squares-1 (PLS-1) and artificial neural network (ANN), were optimized using genetic algorithm (GA) to select the most influential wavelengths, enhancing model performance. A five-level, three-factor design was employed to construct a calibration set with 25 mixtures, utilizing concentration ranges of 3–19, 5–25, and 4–20 µg.mL−1 for MON, RUP, and DES, respectively. An independent validation set was employed to assess the performance of the models. GA significantly improved the PLS-1 and ANN models for RUP and DES, though minimal enhancement was observed for MON. These methods were successfully applied to the simultaneous quantification of the compounds in pharmaceutical formulations and proved useful as stability-indicating assays for RUP, given that DES is a known degradation product. The developed methods offer a valuable tool for impurity profiling and quality control in pharmaceutical analysis. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent antimycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further antimycobacterial drug or regimen optimization, especially in the case of nonreplicating mycobacteria. [ABSTRACT FROM AUTHOR]

In this study, we designed two simple, selective and cost-effective solid-state ion-selective sensors using a polyvinylchloride matrix to detect fexofenadine hydrochloride (FFH) and rupatadine fumarate (RTF) in pharmaceuticals. These sensors utilize the sodium tetraphenyl boron (NaTPB) for ion exchange and β-cyclodextrin for ionophore properties. The FFH sensor shows a linear response within the range of 5 x 10-4 to 2.5 x 10-3 M of FFH at pH levels ranging between 2.5 and 6, exhibiting a Nernstian slope of 56.92 mV decade-1. Similarly, the RTF sensor demonstrates a linear response between 8 x 10-5 and 2.5 x 10-3 M of RTF within the pH range of 2.8-6.4, with a Nernstian slope of 20 mV decade-1. Detection and quantification limits of FFH were found to be 2.5 x 10-4 and 4.5 x 10-4 M, and that of RTF were 2.0 x 10-5 and 6.1 x 10-5 M, respectively. The sensors exhibited excellent selectivity, as indicated by mean percentage recoveries of 100.7 and 99.87 for FFH and RTF, respectively, with a low relative standard deviation (RSD) of less than 2.5%. [ABSTRACT FROM AUTHOR]

Background: Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (PIP5K1A) acts upstream of the Akt regulatory pathway and is abnormally expressed in many types of malignancies. However, the role and mechanism of PIP5K1A in colorectal cancer (CRC) have not yet been reported. In this study, we aimed to determine the association between PIP5K1A and progression of CRC and assess the efficacy and mechanism by which rupatadine targets PIP5K1A. Methods: Firstly, expression and function of PIP5K1A in CRC were investigated by human colon cancer tissue chip analysis and cell proliferation assay. Next, rupatadine was screened by computational screening and cytotoxicity assay and interactions between PIP5K1A and rupatadine assessed by kinase activity detection assay and bio-layer interferometry analysis. Next, rupatadine’s anti-tumor effect was evaluated by in vivo and in vitro pharmacodynamic assays. Finally, rupatadine’s anti-tumor mechanism was explored by quantitative real-time reverse-transcription polymerase chain reaction, western blot, and immunofluorescence. Results: We found that PIP5K1A exerts tumor-promoting effects as a proto-oncogene in CRC and aberrant PIP5K1A expression correlates with CRC malignancy. We also found that rupatadine down-regulates cyclin-dependent kinase 2 and cyclin D1 protein expression by inhibiting the PIP5K1A/Akt/GSK-3β pathway, induces cell cycle arrest, and inhibits CRC cell proliferation in vitro and in vivo. Conclusions: PIP5K1A is a potential drug target for treating CRC. Rupatadine, which targets PIP5K1A, could serve as a new option for treating CRC, its therapeutic mechanism being related to regulation of the Akt/GSK-3β signaling pathway.

Abstract In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.

In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed. [ABSTRACT FROM AUTHOR]

Background: Non‐sedating H1‐antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on‐demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long‐term disease‐modifying effects. Methods: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double‐blind treatment, and 6 weeks of treatment‐free follow‐up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow‐up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU‐related quality of life (QoL), and disease control. Results: At Week 4, disease activity and QoL significantly improved in daily versus OD‐treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow‐up, the disease activity of patients treated OD versus daily was not significantly different. Conclusions: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent antimycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further antimycobacterial drug or regimen optimization, especially in the case of nonreplicating mycobacteria.

Hepatic fibrosis is one of the major worldwide health concerns which requires tremendous research due to the limited outcomes of the current therapies. The present study was designed to assess, for the first time, the potential therapeutic effect of rupatadine (RUP) in diethylnitrosamine (DEN)-induced liver fibrosis and to explore its possible mechanistic actions. For the induction of hepatic fibrosis, rats were treated with DEN (100 mg/kg, i.p.) once weekly for 6 consecutive weeks, and on the 6th week, RUP (4 mg/kg/day, p.o.) was administered for 4 weeks. Treatment with RUP ameliorated changes in body weights, liver indices, liver function enzymes, and histopathological alterations induced by DEN. Besides, RUP amended oxidative stress, which led to the inhibition of PAF/NF-κB p65-induced inflammation, and, subsequently, prevention of TGF-β1 elevation and HSCs activation as indicated by reduced α-SMA expression and collagen deposition. Moreover, RUP exerted significant anti-fibrotic and anti-angiogenic effects by suppressing Hh and HIF-1α/VEGF signaling pathways. Our results highlight, for the first time, a promising anti-fibrotic potential of RUP in rat liver. The molecular mechanisms underlying this effect involve the attenuation of PAF/NF-κB p65/TGF-β1 and Hh pathways and, subsequently, the pathological angiogenesis (HIF-1α/VEGF). [ABSTRACT FROM AUTHOR]

Literature on the effects of second-generation H1-antihistamines on angiogenesis is limited. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Spermatic cord rotation is a common problem in the field of urology, that finally results in necrosis of testicular tissue as well as male infertility. Rupatadine (RUP); a second-generation antihistaminic drug; demonstrated to have a possible protective effect in variable ischemia/reperfusion (I/R) rat models, but its role has not been studied yet in testicular I/R model. The present study investigated RUP ability to ameliorate testicular I/R injury. The study includes four groups (6 rats/group); sham group, sham group pretreated with RUP (6 mg/kg/day; orally) for 14 days, I/R group, and RUP-I/R pretreated group. The results demonstrated that I/R significantly lowered serum testosterone level and testicular tissue content of reduced glutathione. Besides, a significant elevation in malondialdehyde level, hypoxia-inducible factor-1, signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), histamine, and platelet activating factor levels along with an inhibition in testicular tissue level of vascular endothelial growth factor-A (VEGF-A) with an evident increase in caspase-3 immunoexpression in germ cells. Also, I/R significantly lowered p-AKT and mTOR testicular expression. While, RUP-I/R pretreated group showed a reversal in the testicular I/R damaging effects in a significant manner in the all the aforementioned parameters. Based on these findings; RUP was proved to have a possible protective effect in testicular I/R injury via its antioxidant effect and its ability to modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways with improvement in the testicular VEGF-A level. [Display omitted] • Testicular ischemia/reperfusion increased inflammation and cellular damage in rats • Rupatadine (RUP) has a platelet-activating factor receptor blocking activities. • RUP can improve the testicular levels of oxidative stress biomarkers. • RUP can modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways. • RUP improved testicular vasculature by increasing VEGF-A level which rescue testis. [ABSTRACT FROM AUTHOR]

Fluorouracil (5-FU) is a widely used chemotherapeutic agent in various malignant tumors. However, intestinal toxicity is considered the irritant unavoidable adverse effect during the course therapy. The aim of the current study was to screen the effect of a new selective histamine receptor 1 blocker and platelet-activating factor (PAF) blocker on 5-FU induced intestinal toxicity. Five groups (6 rats each) of adult male rats (Wistar) were arranged as follows: (1) control group that was treated with carboxymethylcellulose, (2) a group that received rupatadine (higher dose) only, (3) a group that received 5-FU and (4) and (5) groups that received 5-FU plus lower or higher dose rupatadine, respectively. At end of the experiment, we determined intestinal malondialdehyde (MDA), glutathione reduced (GSH), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin 1β, 6, 10 (IL-1β, IL-6, IL-10), PAF, histamine, myeloperoxidase, cysteine-aspartic acid protease-3 (caspase-3), and nuclear factor kappa B (NF-κB) as well as the histological analysis. 5-FU injection caused marked elevation of MDA, NO, TNF-α, IL-1β, IL-6, PAF, histamine, myeloperoxidase, caspase-3, and NF-κB expressions. The intoxicated animals showed deficient GSH and IL-10 along with significant loss of villi, disorganized crypts, and inflammatory cell infiltration. Rupatadine pretreatment reduced the previously mentioned parameters, preserved a nearly normal intestinal mucosa picture with replenished GSH and elevated IL-10. In conclusion, rupatadine is a dual histamine receptor 1, and a PAF blocker could reduce 5-FU-induced oxidative damage, inflammation, apoptosis, and ulceration of the intestinal epithelium. Rupatadine may be a valuable modality to decrease 5-FU induced intestinal mucositis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is an autoimmune disease with a strong neuroinflammatory component that contributes to severe demyelination, neurodegeneration and lesions formation in white and grey matter of the spinal cord and brain. Increasing attention is being paid to the signaling of the biogenic amine histamine in the context of several pathological conditions. In multiple sclerosis, histamine regulates the differentiation of oligodendrocyte precursors, reduces demyelination, and improves the remyelination process. However, the concomitant activation of histamine H1–H4 receptors can sustain either damaging or favorable effects, depending on the specifically activated receptor subtype/s, the timing of receptor engagement, and the central versus peripheral target district. Conventional drug development has failed so far to identify curative drugs for multiple sclerosis, thus causing a severe delay in therapeutic options available to patients. In this perspective, drug repurposing offers an exciting and complementary alternative for rapidly approving some medicines already approved for other indications. In the present work, we have adopted a new network-medicine-based algorithm for drug repurposing called SAveRUNNER, for quantifying the interplay between multiple sclerosis-associated genes and drug targets in the human interactome. We have identified new histamine drug-disease associations and predicted off-label novel use of the histaminergic drugs amodiaquine, rupatadine, and diphenhydramine among others, for multiple sclerosis. Our work suggests that selected histamine-related molecules might get to the root causes of multiple sclerosis and emerge as new potential therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

5-fluorouracil (5-FU) is a widely used chemotherapeutic drug, but its hepatotoxicity challenges its clinical use. Thus, searching for a hepatoprotective agent is highly required to prevent the accompanied hepatic hazards. The current study aimed to investigate the potential benefit and mechanisms of action of rupatadine (RU), a Platelet-activating factor (PAF) antagonist, in the prevention of 5-FU-related hepatotoxicity in rats. Hepatotoxicity was developed in male albino rats by a single 5-FU (150 mg/kg) intra-peritoneal injection on the 7th day of the experiment. RU (3 mg/kg/day) was orally administrated to the rodents for 10 days. Hepatic toxicity was assessed by measuring both liver and body weights, serum alanine aminotransferase and aspartate aminotransferase (ALT and AST), hepatic oxidative stress parameters (malondialdehyde (MDA), nitric oxide levels (NOx), reduced glutathione (GSH), superoxide dismutase (SOD)), and heme oxygenase-1 (HO-1). Inflammatory markers expressions (inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukins; IL-1B, IL-6), the apoptotic marker (caspase-3), and PAF were measured in the hepatic tissue. 5-FU-induced hepatotoxicity was proved by the biochemical along with histopathological assessments. RU ameliorated 5-FU-induced liver damage as proved by the improved serum ALT, AST, and hepatic oxidative stress parameters, the attenuated expression of hepatic pro-inflammatory cytokines and PAF, and the up-regulation of HO-1. Therefore, it can be concluded that RU pretreatment exerted a hepatoprotective effect against 5-FU-induced liver damage through both its powerful anti-inflammatory, antioxidant, and anti-apoptotic effect. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (PIP5K1A) acts upstream of the Akt regulatory pathway and is abnormally expressed in many types of malignancies. However, the role and mechanism of PIP5K1A in colorectal cancer (CRC) have not yet been reported. In this study, we aimed to determine the association between PIP5K1A and progression of CRC and assess the efficacy and mechanism by which rupatadine targets PIP5K1A. Firstly, expression and function of PIP5K1A in CRC were investigated by human colon cancer tissue chip analysis and cell proliferation assay. Next, rupatadine was screened by computational screening and cytotoxicity assay and interactions between PIP5K1A and rupatadine assessed by kinase activity detection assay and bio-layer interferometry analysis. Next, rupatadine's anti-tumor effect was evaluated by in vivo and in vitro pharmacodynamic assays. Finally, rupatadine's anti-tumor mechanism was explored by quantitative real-time reverse-transcription polymerase chain reaction, western blot, and immunofluorescence. We found that PIP5K1A exerts tumor-promoting effects as a proto-oncogene in CRC and aberrant PIP5K1A expression correlates with CRC malignancy. We also found that rupatadine down-regulates cyclin-dependent kinase 2 and cyclin D1 protein expression by inhibiting the PIP5K1A/Akt/GSK-3β pathway, induces cell cycle arrest, and inhibits CRC cell proliferation in vitro and in vivo. PIP5K1A is a potential drug target for treating CRC. Rupatadine, which targets PIP5K1A, could serve as a new option for treating CRC, its therapeutic mechanism being related to regulation of the Akt/GSK-3β signaling pathway. [Display omitted] • PIP5K1A kinase is a promising drug target for CRC. • Rupatadine inhibits the PIP5K1A/Akt/GSK-3β pathway to exert antitumor effects. • Rupatadine can be used as a new drug choice for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to analyse the potential effect of rupatadine (RUP) on ulcerative colitis (UC) induced by acetic acid (AA). Methods Forty male adult Wistar rats were divided into five groups: Control group: received vehicles for 14 days; AA model group: received AA at the 13th day; Sulfasalazine (SLZ) + AA group: received SLZ (250 mg/kg) for 14 days and AA at the 13th day; RUP-3 + AA group: received RUP (3 mg/kg/day) for 14 days and AA at the 13th day; and RUP-6 + AA group: received RUP (6 mg/kg/day) for 14 days and AA at the 13th day. Evidence of UC was assessed both macroscopically and microscopically. Oxidative stress markers (total antioxidant capacity and malondialdehyde), antioxidant enzyme (superoxide dismutase), histamine and platelet-activating factor (PAF) were determined. Immunohistochemical estimations of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were done. Key findings The AA group showed evidence of UC that was associated with a significant increase in oxidative stress, histamine and PAF levels with significant elevation in colonic VEGF and IL-6 immuno-expressions. RUP, in a dose-dependent manner, significantly ameliorated UC. Conclusion RUP protects against UC by reducing oxidative stress and by regulating the PAF/IL-6/VEGF pathway. [ABSTRACT FROM AUTHOR]

Purpose: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). Methods: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15–25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. Results: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. Conclusion: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018 [ABSTRACT FROM AUTHOR]

Abstract Background The clinical efficacy of rupatadine in terms of responders has not been previously explored in perennial allergic rhinitis (PAR). Methods This pooled analysis included data from 6 randomised, double-blind, placebo-controlled trials conducted in PAR patients treated with rupatadine 10 mg or 20 mg, or placebo. Participants were aged ≥ 18 years, with diagnosis of PAR and a Total 4 Nasal Symptom Score (T4NSS) ≥ 5. We evaluated the T4NSS and Total 5 Symptom Score (T5SS) for 28 days of treatment, the responder proportion (50% and 75% response), and the time to response. Results Efficacy data from 1486 patients were analysed: 585 received placebo, 682 rupatadine 10 mg, and 219 rupatadine 20 mg. Compared with placebo, rupatadine promoted greater symptom improvements and higher responder proportions (50% and 75% response) for T4NSS and T5SS over 28 days. Symptom improvements and responder proportions were higher in the rupatadine 20 mg group vs the 10 mg group. The time to response was shorter in the rupatadine 20 mg group vs the 10 mg group for T4NSS (16 and 9 days for the 50% and 75% responses, respectively) and for T5SS (13 and 8 days for the 50% and 75% responses, respectively). Conclusions Rupatadine was efficacious in reducing allergic rhinitis symptoms, showing high responder proportions. The faster and stronger effect of rupatadine 20 mg may suggest its use in patients with severe PAR or not responding to the standard dose.

Allergic Rhinitis is basically a chronic disease that decreases quality of life. Antihistaminics have been used for the first time in allergic rhinitis. In the search for an alternative treatment in resistant allergic rhinitis, Montelukasts and their combinations have been used. Randomized double-blind controlled study. In our study, the effect on the quality of life of the compounds used recently be compared after 3 months of treatment. In this study, 7 groups of 40 patients, 18-65 years old were planned for each group. The number of females and males was equal in each group (20). The patients in group A and group B will be called for checks after 3 months of medical treatment in the C-D-E-F-G-H group without treatment for 3 months. The patients in Group C received 10 mg Rupatadin Fumarate tablets orally (1 * 1 single dose) before bedtime, 5 mg Levosetirizine Dihydrochloride tablets in the patients in Group D orally (1 * 1 single dose) before bedtime, 10 mg Montelukast Sodium tablets in patients in Group E Before oral (1 * 1 single dose), patients in Group F 5 mg Desloratadin + 10 mg Montelukast Sodium tablets orally (1 * 1 single dose) before bedtime, and patients in Group G Levocetirizine Dihydrochloride + 10 mg Montelukast Sodium tablet orally before bedtime (1 * 1 single dose) will be given. These treatments will continue for 3 months without interruption. The Rinokonjucivations Quality of Life Questionnaire (RQLQ) will be completed with a total of 28 questions. No significant superiority of the Rupatadine molecule to levocetirizine was detected. The score of the Montelukast areas was significantly low when compared to the Rupatadine and Levosetirizine groups. Combined Montelukastes were found to be much more effective than single antihistaminics and single montelukast. There was no difference in quality of life between the combined Montelukast. Antihistaminics are the first treatment option in patients with allergic rhinitis,In resistant cases, combinations with montelukast should be used. [Med-Science 2019; 8(4.000): 967-70]

Two green-sensitive spectrofluorometric methods were investigated for assay of rupatadine (RUP) [method I] and its binary mixture with montelukast (MKT) [method II]. Method I depends on measuring native fluorescence of RUP in the presence of 0.10 M H2SO4 and 0.10%w/v sodium dodecyl sulfate at 455 nm after excitation at 277 nm. The range of the first method was 0.20–2.00 µg ml−1 with detection and quantitation limits of 59.00 and 179.00 ng ml−1, respectively. Method II depends on the first derivative synchronous spectrofluorometry. The derivative intensities were measured for the two drugs in an aqueous solution containing Mcllvaine's buffer pH 2.60 at fixed Δλ of 140 nm. Each drug was estimated at zero-contribution of the other. The intensity was measured at 261 and 371 nm for RUP and MKT, respectively. The method was linear over 0.10–4.00 and 0.20–1.60 µg ml−1 with limits of detection 31.00 and 66.00 ng ml−1 and limits of quantitation 94.00 and 200.00 ng ml−1 for RUP and MKT, respectively. The method was extended to determine this mixture in laboratory-prepared mixtures and combined tablets. Method validation was performed according to ICH guidelines. Statistical interpretation of data revealed good agreement with the comparison method. Method greenness was confirmed by applying three different assessment tools.

Background: Allergic rhinitis (AR) and chronic urticaria, both are treated in children with doses of second generation of antihistamines that have been mostly based on extrapolation of data obtained in adults. The objectives of this work were to develop a model to explain the pharmacokinetics (PK) of rupatadine, a second generation antihistamine, administered to children 2− 11 years old and to calculate the non-compartmental PK parameters for two groups of age (2– 5 and 6– 11 years old) based on the individual Bayesian estimates from the selected model. Methods: Data from two PK studies with rupatadine oral solution (1 mg/mL) were pooled: Study A, an extensive blood sampling study performed in 11 children (6– 11 years old) who received a single oral dose of rupatadine; and Study B, a sparse blood sampling study in 40 children (2– 5 years old) receiving multiple oral doses. A simultaneous population PK model was developed using data available for all children. Using individual Bayesian estimates from the selected model, steady-state plasma concentrations for both studies were simulated and the non-parametric PK parameters were calculated for two age groups: 2– 5 years (subgroup I) and 6– 11 years (subgroup II). Results: A two-compartment model with first-order absorption and elimination with clearance depending on body weight, better described the PK of rupatadine for 2– 11 year old children. The plasma clearance dependence on weight was linear. The mean (SD) non-compartment PK parameters calculated using simulated plasma profiles at steady state were: Cmax, 2.54 (1.26) vs 1.96 (0.52) ng/mL; AUC0-24h, 10.74 (3.09) vs 10.38 (4.31) ng/mL/h; and t1/2, 12.28 (3.09) vs 15.94 (4.09) h, for children 6– 11 and 2– 5 years old, respectively. Conclusions: The PK of rupatadine depends on the weight of paediatric patients but not on their age. The dosage strategy adjusted by body weight in children 2– 11 years old (2.5 mL if weight 10– 25 kg, and 5 mL if ≥ 25 kg) provides similar exposure between the two groups of age, and to that obtained in adults with the 10 mg dose tablet formulation. [ABSTRACT FROM AUTHOR]

Abstract Objectives The effect of rupatadine, a novel H1 antihistamine with platelet‐activating factor antagonist activity, had been demonstrated for itching in Japanese patients with chronic spontaneous urticaria, dermatitis, or pruritus in a 12‐month, open‐label clinical trial (JapicCTI‐152787). However, patients could have received an updose at various timings due to distinct reasons in the study; timing of updose was not evaluated. This study aimed to elucidate the relationship between performance of rupatadine and timing of updose. Methods For 206 enrolled patients was evaluated the total pruritus score (TPS) to Week 2 with 10 mg rupatadine. From Week 3 to Week 52, rupatadine was updosed to 20 mg accordingly. Subpopulation was categorized by absence/presence of updosing and timing of updose (Week 3 or ≥Week 5). Results Reduction of TPS from baseline to Week 2 in patients updosed at Week 3 was significantly lower than those given an updose at ≥Week 5 and fixed dose. However, significant improvement in the change in mean TPS from 1 week pre‐updose to the second week post‐updose was achieved regardless of updose timing, scoring −0.903 for Week 3 and −0.983 for ≥Week 5 (P

Abstract Background Different clinical trials showed the superior efficacy of rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. Methods This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Results Data from 1470 patients were analyzed: 332 treated with placebo, 662 with rupatadine 10 mg and 476 with rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in rupatadine groups compared to the placebo group across the visits. Among rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the rupatadine 20 mg group than in the rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. Conclusions This responder analysis confirms the superior efficacy of rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group.

Disruption of Th17/Tregs homeostasis plays a crucial role in governing the immune response during myocardial fibrosis and its progression to heart failure. The present study aimed to assess for the first time the possible protection afforded by rupatadine against isoproterenol-induced heart failure in rats. It also explored the role of PI3k/Akt as a possible mechanistic pathway, through which rupatadine could modulate Th17/Tregs balance to display its effect. Isoproterenol (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively and rupatadine (4 mg/kg/day) was then given orally for 14 days with or without wortmannin (PI3K/Akt inhibitor). Rupatadine succeeded to completely ameliorate isoproterenol-induced cardiac dysfunction as demonstrated by improvements of electrocardiographic and echocardiographic measurements. Moreover, rupatadine prevented the marked elevation of PAF and oxidative stress in addition to Th17 promoting cytokines (IL-6, IL-23, and TGF-β). Accordingly, rupatadine prevented Th17 stimulation or expansion as indicated by increased Foxp3/RORγt ratio and decreased production of its pro-inflammatory cytokine (IL-17). Rupatadine treatment mitigated isoproterenol-induced activation of STAT-3 signaling and the imbalance in p-Akt/total Akt ratio affording marked decrease in atrogin-1 and apoptotic biomarkers. Finally, this therapy was effective in averting cardiac troponin loss and reverting the histological alterations as assessed by myocardial fibrosis and hypertrophy grading. Contrariwise, co-administration of wortmannin mostly attenuated the protective effects of rupatadine affording more or less similar results to that of isoproterenol-untreated rats. In conclusion, rupatadine could be an effective therapy against the development of isoproterenol-induced heart failure where PI3K/Akt pathway seems to play a crucial role in its protective effect.

In this study, spectrofluorimetric and resonance Rayleigh scattering techniques were applied for the first time for determination of rupatadine through two validated methods. The proposed methods were based on a facile association complex formation between rupatadine and erythrosin B reagent in acidic medium. Spectrofluorimetric determination relied on the quenching effect of rupatadine on the fluorescence intensity of erythrosin B at 556 nm (excitation = 530 nm). Conversely, the resonance Rayleigh scattering (RRS) method relied on enhancement in the resonance Rayleigh scattering spectrum of erythrosin B at 344 nm after the addition of rupatadine. The developed methods produced linear results over ranges 0.15−2.0 μg/ml and 0.1−1.5 μg/ml, with detection limits of 0.030 μg/ml and 0.018 μg/ml for the spectrofluorimetric method and the RRS method, respectively. All reaction conditions for rupatadine–erythrosin B formation were optimized experimentally and both methods were validated according to International Council for Harmonisation guidelines. The developed methods were applied to estimate rupatadine content in its pharmaceutical tablet dosage form with acceptable recoveries. Furthermore, a content uniformity test for the commercial rupatadine tablets was successfully applied by the suggested spectroscopic methods according to United States Pharmacopeia guidelines. [ABSTRACT FROM AUTHOR]

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Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID‐19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID‐19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL‐1β and IL‐6, which may contribute to COVID‐19 and especially SARS. The histamine‐1 receptor antagonist rupatadine was developed to have anti‐PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID‐19 prophylaxis alone or together with other PAF‐inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti‐inflammatory, and anti‐PAF actions. [ABSTRACT FROM AUTHOR]

Rituximab‐associated infusion reactions (IRs) are significant burdens on oncology patients, caregivers and healthcare providers. We evaluated whether montelukast and rupatadine improve rituximab delivery, decrease frequency/severity of IRs and the number of medications used to control IRs. Using a nonrandomized clinical study design, we assessed adult rituximab naïve patients with B‐cell lymphoid malignancies from January 2017 to July 2019. Prior to the first rituximab infusion patients received one of the premedication regimens: (i) standard premedications, diphenhydramine hydrochloride and acetaminophen ("SP" group); (ii) SP + montelukast ("M" group); (iii) SP + rupatadine ("R" group); (iv) SP + rupatadine + montelukast Schedule 1 ("M + R Schedule 1" group); (v) SP + rupatadine + montelukast Schedule 2 ("M + R Schedule 2" group). A total of 223 patients with a median age of 69 years were assessed. Demographics and treatment groups were comparable among all five groups. Mean rituximab infusion time was 290 min in the SP group versus 273, 261, 243 and 236 min in the M, R, M + R Schedule 1 and M + R Schedule 2 groups, respectively. The incidence of rituximab IRs was 75% in the SP group versus 44, 41, 22 and 22% in the M, R, M + R Schedule 1 and M + R Schedule 2 groups, respectively. The median reaction grade was 2 in the SP group and 0 in all other groups. The median number of rescue medications was 3 in the SP group and 0 in all other groups. In conclusion, montelukast and rupatadine significantly improved rituximab delivery, decreased the rate and severity of IRs and reduced the need for rescue medications. What's new? Rituximab is an essential component of chemotherapeutic regimens for B‐Cell lymphoproliferative disorders. However, Rituximab delivery is also associated with frequent infusion reactions that range from mild to fatal. Here, the authors found that premedication with Montelukast and Rupatadine decreased Rituximab infusion time by over 20%. Compared to standard pre‐medications, the rate of Rituximab‐associated infusion reactions decreased from 75% to 22% with Montelukast and Rupatadine. The median severity of reactions also decreased from 2 to 0. The average use per patient of the five most common rescue medications decreased up to 73%. Montelukast and Rupatadine did not affect response to chemoimmunotherapy. [ABSTRACT FROM AUTHOR]

The role of histamine and platelet activating factor (PAF) as involved mediators in the pathophysiology of diabetic complications, in particular diabetic nephropathy (DN), has become a new focus of concern. Accordingly, the present study designed to explore the effect of rupatadine (RUP), a dual antagonist of histamine (H1) and PAF, on the progression of experimentally induced DN in rats. Rats were divided into five groups: control, RUP alone, streptozotocin (STZ)-diabetic model, STZ/RUP (3 mg/kg/day), and STZ/RUP (6 mg/kg/day). Treatment has continued for 4 weeks after diabetes confirmation. At the end of the study, serum was collected for measurement of glucose, insulin, urea, creatinine, histamine, and PAF. Renal tissue homogenates were prepared for measuring oxidative stress indices, tumor necrosis factor (TNF-α), cystatin C, and p21. Moreover, immunohistochemical expression of transforming growth factor-β1 (TGF-β1) and p53 along with histological pictures was also conducted. Antagonizing H1 and PAF receptors by RUP ameliorated the experimentally induced DN as evident by decreasing all serum parameters augmented by STZ together with improvement of the histopathological picture. RUP administration also improved oxidative-antioxidative agents with reduction in the anti-inflammatory marker, TNF-α. Additionally, the immunohistochemical expression of the fibrosis marker; TGF-β1, was also decreased. STZ-induced DN showed a p21/p53-dependent induction of premature senescence and RUP administration decreased the expression of p21 and p53 levels in injured renal tissue. RUP represents a novel promising drug to prevent DN complicated diabetes probably via its inhibitory effect on H1 and PAF receptors. The renal protection was also related to the anti-inflammatory and antioxidant roles and PAF-facilitated senescence effect via p21/p53 signaling. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy of rupatadine in terms of responders has not been previously explored in perennial allergic rhinitis (PAR). Methods: This pooled analysis included data from 6 randomised, double-blind, placebo-controlled trials conducted in PAR patients treated with rupatadine 10 mg or 20 mg, or placebo. Participants were aged ≥ 18 years, with diagnosis of PAR and a Total 4 Nasal Symptom Score (T4NSS) ≥ 5. We evaluated the T4NSS and Total 5 Symptom Score (T5SS) for 28 days of treatment, the responder proportion (50% and 75% response), and the time to response. Results: Efficacy data from 1486 patients were analysed: 585 received placebo, 682 rupatadine 10 mg, and 219 rupatadine 20 mg. Compared with placebo, rupatadine promoted greater symptom improvements and higher responder proportions (50% and 75% response) for T4NSS and T5SS over 28 days. Symptom improvements and responder proportions were higher in the rupatadine 20 mg group vs the 10 mg group. The time to response was shorter in the rupatadine 20 mg group vs the 10 mg group for T4NSS (16 and 9 days for the 50% and 75% responses, respectively) and for T5SS (13 and 8 days for the 50% and 75% responses, respectively). Conclusions: Rupatadine was efficacious in reducing allergic rhinitis symptoms, showing high responder proportions. The faster and stronger effect of rupatadine 20 mg may suggest its use in patients with severe PAR or not responding to the standard dose. [ABSTRACT FROM AUTHOR]

Objective: Long-term safety and efficacy of 10- and 20-mg rupatadine in Japanese patients with perennial allergic rhinitis (PAR) were investigated in a 52-week open-label study (JapicCTI-152952, clinicaltrials.jp). Methods: The rupatadine dose was fixed to 10 mg once daily for the first 2 weeks. Thereafter, the study investigator was allowed to increase the dosage to 20 mg if the response was insufficient. Safety was evaluated on the basis of treatment-emergent adverse events, laboratory findings, and vital sign measurements. The primary efficacy endpoint was changed from baseline to Week 2 in the total 4 nasal symptom score. Secondary efficacy endpoints included changes over time in ocular symptoms, patient and physician clinical overall impression, and patient quality-of-life. Results: Seventy-two immunoglobulin E positive patients (mean age = 32.1 years), consisting of 58 adults (age ≥ 18 years) and 14 adolescents (12–17 years), were enrolled. Ninety-four treatment-emergent adverse events were reported in 48 patients (66.7%), including nine adverse drug reactions in nine patients (12.5%). The most frequently reported adverse drug reaction was somnolence (9.7%). The primary and secondary efficacy endpoints demonstrated a statistically significant clinical benefit with rupatadine. The rupatadine dose was increased from 10 to 20 mg in 36 patients (50.0%), which resulted in better symptom management. Conclusions: Rupatadine 10- and 20-mg once-daily doses were well tolerated in long-term use. Updosing to 20 mg is a reasonable option in PAR patients whose symptoms cannot be controlled effectively by the 10-mg dose. [ABSTRACT FROM AUTHOR]

The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.

The article presents the European Guidelines for the Diagnostics and Management of Urticaria (revised in 2013) and new data on the physiopathology of urticaria related to the role of the platelet-activating factor (PAF) activating mast cells, attracting eosinophils and neutrophils, improving vascular permeability (it is more potent than histamine by 1,000 times) and mucosal edema, and increasing the level of pro-inflammatory cytokines. The data promoted the creation of a new rupatadine molecule, which blocks histamine and PAF receptors at the same time improving the therapeutic effect during urticaria treatment as compared to other antihistamine drugs. The author presents the study results confirming the efficacy and safety of rupatadine.

Second generation antihistamine drugs are mainly used for the therapy of patients suffering from urticaria; however, they are efficient in 45-60% of cases only. New drugs for treatment of urticaria need to be developed and implemented, and second generation antihistamine drug Rupatadine is one of them. At the same time, Rupatadine efficiently inhibits the inflammatory action of the platelet-activating factor. Due to its double action, Rupatadine used perorally in the dose of 10 mg once a day is an efficient drug for treatment of urticaria, and its safety was confirmed by clinical trials.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation., Competing Interests: Disclosure and potential conflicts of interest: II and LC are employees of BIOHORM S.L. SC and AF are employees of NOUCOR HEALTH S.A. The authors declare no other conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/12/dic.2023-9-5-COI.pdf, (Copyright © 2024 Izquierdo I, Casas L, Cabrera S, Fernandez A.)

Objectives: The effect of rupatadine, a novel H1 antihistamine with platelet‐activating factor antagonist activity, had been demonstrated for itching in Japanese patients with chronic spontaneous urticaria, dermatitis, or pruritus in a 12‐month, open‐label clinical trial (JapicCTI‐152787). However, patients could have received an updose at various timings due to distinct reasons in the study; timing of updose was not evaluated. This study aimed to elucidate the relationship between performance of rupatadine and timing of updose. Methods: For 206 enrolled patients was evaluated the total pruritus score (TPS) to Week 2 with 10 mg rupatadine. From Week 3 to Week 52, rupatadine was updosed to 20 mg accordingly. Subpopulation was categorized by absence/presence of updosing and timing of updose (Week 3 or ≥Week 5). Results: Reduction of TPS from baseline to Week 2 in patients updosed at Week 3 was significantly lower than those given an updose at ≥Week 5 and fixed dose. However, significant improvement in the change in mean TPS from 1 week pre‐updose to the second week post‐updose was achieved regardless of updose timing, scoring −0.903 for Week 3 and −0.983 for ≥Week 5 (P < 0.001). Conclusions: The results inferred the inclusivity of patients who either updosed during the earlier phase due to lack of efficacy, or later due to aggravation of symptoms. The results of this subgroup analysis produced evidence of appropriateness for using 10 mg rupatadine as the starting dose, and evaluating the necessity of updose to 20 mg during the first 2 weeks for nonresponsive patients. [ABSTRACT FROM AUTHOR]

• Rupatadine is a novel second-generation antihistamine. • Rupatadine showed long-term efficacy for managing itching in Japanese patients. • Updosing to 20 mg reduced pruritus of patients with insufficient effect at 10 mg. • Rupatadine was safe in long-term use in Japanese patients. • No noteworthy safety signals due to rupatadine were observed in adolescents. Rupatadine is a novel H1 antihistamine with platelet-activating factor antagonist activity. Its efficacy and safety on pruritic skin diseases have been demonstrated by 10 mg/day rupatadine in a two weeks clinical trial. To investigate the long-term efficacy and safety of rupatadine in the management of pruritus, and the clinical effect of updosing to 20 mg in Japanese adult and adolescent patients. In this 52-week, multicenter, open-label clinical trial (JapicCTI-152787), 206 patients (132, eczema or dermatitis; 58, pruritus; and 16, chronic spontaneous urticaria) received the study medication. The primary efficacy endpoint was change from baseline in the total pruritus score to Week 2 by treatment with rupatadine 10 mg once daily. From Week 3 to Week 52, rupatadine updosing to 20 mg was allowed. The mean [95% CI] change from baseline to Week 2 in the total pruritus score was −1.241 [−1.450, −1.033] (paired t test, P < 0.001). The therapeutic effect persisted up to Week 52 (paired t test, P < 0.001). Adverse drug reactions (ADRs) were reported at an overall incidence of 18.0% (45 events in 37 patients). No serious or clinically significant ADRs were reported. Somnolence was the most common ADR (14.1%). This clinical trial demonstrated the short- and long-term benefits of rupatadine in the management of patients with chronic spontaneous urticaria, dermatitis, and pruritus. Rupatadine 10 and 20 mg doses are effective for the treatment of itch in adults and adolescents, and can be used safely on a long-term basis. [ABSTRACT FROM AUTHOR]

Abstract Background Rupatadine is a novel non-sedating second-generation H 1 -antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). Methods This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12–64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Results Nine hundred patients were randomly assigned to placebo, rupatadine 10 mg, or rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between rupatadine and placebo was −1.085 for 10 mg, and −1.415 for 20 mg (analysis of covariance, both P < 0.001). The rates of adverse events were 6.6%, 14.1%, and 15.0% for placebo, rupatadine 10 mg, and rupatadine 20 mg, respectively. Somnolence was most frequently reported: 7.0% for rupatadine 10 mg and 7.3% for rupatadine 20 mg. No serious adverse drug reactions were observed, and no adverse events resulted in premature discontinuation. Conclusions Rupatadine 10 and 20 mg were significantly superior to placebo in improving nasal and ocular symptoms of SAR, and were well tolerated. [ABSTRACT FROM AUTHOR]

Abstract Background Rupatadine, a novel nonsedating second-generation H1-antihistamine with antiplatelet-activating factor activity, has been used in the treatment of allergic rhinitis and urticaria in European countries since 2003. However, its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU) are unknown. Methods We conducted a prospective, multicenter, randomized, placebo-controlled, double-blind study in adolescent and adult CSU outpatients aged 12 to < 65 years (JAPIC-CTI No. 152786). Overall, 94, 91, and 92 eligible patients orally received placebo, rupatadine 10 mg, and 20 mg once daily for 2 weeks, respectively. The primary endpoint was change from baseline to the second week of treatment in total pruritus score (TPS, sum of daytime and nighttime pruritus scores). Results The results yielded a least squares mean TPS difference of −1.956 between rupatadine 10 mg versus placebo, and −2.121 between rupatadine 20 mg versus placebo (analysis of covariance, both P < 0.001). The incidence of adverse events was 8.5% for placebo, 20.9% for rupatadine 10 mg, and 17.4% for rupatadine 20 mg. Somnolence was the only adverse drug reaction to rupatadine reported in 2 or more subjects. No serious or clinically significant adverse events were observed. Conclusions The primary and secondary efficacy endpoints consistently favored rupatadine 10 and 20 mg doses over the placebo. No noteworthy dose-related increase in the incidence of adverse drug reactions was observed. Rupatadine is safe and effective at a dose of 10 mg once daily, and can be safely increased to 20 mg once daily, as necessary. [ABSTRACT FROM AUTHOR]

Background: Different clinical trials showed the superior efficacy of rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. Methods: This study is a pooled analysis of data of seven randomized, double‐blind, placebo‐controlled SAR studies comparing responder proportions upon treatment with rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near‐to‐complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Results: Data from 1470 patients were analyzed: 332 treated with placebo, 662 with rupatadine 10 mg and 476 with rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in rupatadine groups compared to the placebo group across the visits. Among rupatadine‐treated patients, those receiving 20 mg compared favourably for both cut‐off responses. The time to achieve a proportion of responders was shorter in the rupatadine 20 mg group than in the rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near‐to‐complete response for both symptom scores was higher in rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. Conclusions: This responder analysis confirms the superior efficacy of rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose‐dependent manner, with faster and higher response rates in the 20 mg group. [ABSTRACT FROM AUTHOR]

Introduction : Second generation antihistamines are key medicines in the treatment of allergic diseases such as allergic rhinitis and allergic conjunctivitis. Aim of the research: To compare the effectiveness of selected antihistamines and frequency of side effects in the course of their therapy in the patient opinion. Material and methods : The study was conducted on a group of 40 patients taking rupatadine, bilastine, levocetirizine and fexofenadine. The method of diagnostic survey was used, having the character of a preliminary examination in view of the small number of people involved in the study. Results: Among the 40 patients, side effects of the medicines only appeared in 3 respondents, which is 1.2%. Conclusions : The new generation antihistamines in light of our studies appear to be safe and associated with few side effects. Due to the small number of surveyed people we treat these tests as preliminary to further analysis of the effectiveness of selected antihistamines.

Objective: To compare efficacy, safety and cost-effectiveness of rupatadine and olopatadine in patients of chronic spontaneous urticaria. Materials and Methods: A 6-week, single-centered, randomized, double blind, parallel group comparative clinical study was conducted on patients with chronic spontaneous urticaria. Following inclusion and exclusion criteria, 60 patients were recruited and were randomized to two treatment groups and received the respective drugs for 6 weeks. At follow-up, parameters assessed were mean total symptom score (MTSS) calculated by adding the mean number of wheals (MNW) and the mean pruritus score (MPS), number of wheals, size of wheal, scale for interference of wheals with sleep (SIWS). Results: Both the drugs significantly reduced the MTSS, number of wheals, size of wheal, scale for interference of wheals with sleep, but olopatadine was found to be superior. In olopatadine group, there was significantly higher reduction in MTSS (p = 0.01), Number of wheals (P < 0.05), Size of wheals (p < 0.05), Scale for intensity of erythema (p < 0.05) and change in eosinopils count (p = 0.015) than that of rupatadine. Incidence of adverse effects was found to be less in olopatadine group when compared with rupatadine group. Cost effectiveness ratio was less in olopatadine group as compared to rupatadine group throughout the treatment. Conclusions: Olopatadine is a better choice in chronic spontaneous urticaria in comparison to rupatadine due to its better efficacy, safety and cost effectiveness profile.