ArticleLiterature Review

Rupatadine: A review of its use in the management of allergic disorders

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Abstract

Rupatadine (Rupafin, Rinialer, Rupax, Alergoliber) is a selective oral histamine H(1)-receptor antagonist that has also been shown to have platelet-activating factor (PAF) antagonist activity in vitro. It is indicated for use in seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU) in patients aged >/=12 years. Clinical trials show that rupatadine is an effective and generally well tolerated treatment for allergic rhinitis and CIU. It has a rapid onset of action and a prolonged duration of activity. Importantly, it has no significant effect on cognition, psychomotor function or the cardiovascular system. Once-daily rupatadine significantly improves allergic rhinitis symptoms in patients with SAR, PAR or persistent allergic rhinitis (PER) compared with placebo, and provides similar symptom control to that of loratadine, desloratadine, cetirizine or ebastine. In patients with CIU, longer-term use of rupatadine improves CIU symptoms to a greater extent than placebo. It is as well tolerated as other commonly used second-generation H(1)-receptor antagonists. Thus, the introduction of rupatadine extends the range of oral agents available for the treatment of allergic disorders, including allergic rhinitis and CIU.

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... Rupatadine, an N-alkyl pyridine derivative, is a selective oral histamine H 1 -receptor inverse agonist, indicated for symptomatic treatment of allergic rhinitis and urticaria in adults and children C2 years [8,9]. The drug exhibits strong and balanced antagonist activities towards both histamine H 1 -and platelet-activating factor (PAF) receptors (for review see: [10][11][12][13][14][15][16]). Both histamine and PAF are held to importantly contribute to the signs and symptoms of CSU, i.e., itchy wheals and angioedema [17]. ...
... Rupatadine has undergone long-term testing (up to 1 year) in compliance with ICH and EMA guidelines confirming its good safety profile [21][22][23]. At the licensed daily oral dose of 10 mg, rupatadine has no clinically relevant effects on the cardiovascular system, cognitive function or psychomotor function [10,14]. The current guideline on the management of urticaria patients recommends aiming for a complete symptom relief [1]. ...
... by the subjective assessments of patients and physicians. The favorable tolerability of rupatadine at oral doses of 10 and 20 mg daily has been evidenced in several clinical studies (reviewed by[10][11][12][13][14][15][16]). The most commonly (percentages of AEs according to[8]). ...
Article
Introduction Chronic spontaneous urticaria (CSU) is a common and hard to treat condition associated with a substantial negative impact on patients’ quality of life (QoL). Clinical studies have shown that rupatadine is effective and safe in the treatment of CSU, but data from routine clinical care are scarce. Therefore, we assessed the effectiveness and tolerability of rupatadine in established dosages on CSU activity and patients’ QoL in a routine daily practice setting. Methods This was an open, prospective, non-interventional study performed in 146 dermatological practices in Germany. CSU patients for whom treatment with rupatadine was indicated were eligible to participate. Key symptoms of urticaria activity and their impact on patients’ QoL were assessed at the beginning and the end of treatment. Adverse events (AEs) and withdrawals, as well as the dosage regimens chosen, were documented. Patients and physicians were requested to rate effectiveness and tolerability of therapy at the final visit. All statistical analyses were descriptive. Results The majority of the 660 patients screened to be treated (median age 44 years, IQR = 31–59 years, n = 654) received rupatadine 10 mg tablets once (477 patients) or twice (105 patients) daily for a median time of 28 days. After treatment, 93.2% of the patients (606/650) reported a clear overall improvement of symptoms. Rupatadine significantly reduced the urticaria activity score (UAS7) as well as the frequency and severity of existing angioedema episodes. Similarly all domains of the urticaria-specific QoL questionnaire (CU-Q2oL) were markedly improved. The majority of physicians and patients rated rupatadine treatment as effective and well tolerated. There were 39 (5.9%) early treatment withdrawals, and 21 patients (3.2%) experienced AEs. Conclusion Rupatadine when given according to the routine treating schemes improves symptoms and CU-Q2oL of CSU patients; the drug is also safe and well tolerated. Funding Dr. R. Pfleger GmbH.
... Rupatadine exhibits a safety profile in children similar to that of other secondgeneration antihistamines such as cetirizine, levocetirizine, desloratadine or fexofenadine (22)(23)(24)(25) and was generally well tolerated. The overall incidence of adverse events in children aged 6-11 yr treated with rupatadine paediatric oral solution 1 mg/ml was lower than that reported in adults and adolescents with rupatadine tablets (13,26), and almost no adverse reactions were reported with an incidence higher than 1%. Of note, the incidence of treatment-related somnolence, an important consideration from the viewpoint of reduced academic performance in school children, was very low (1.1% in the rupatadine group) and markedly lower than that observed in adults (13,26). ...
... The overall incidence of adverse events in children aged 6-11 yr treated with rupatadine paediatric oral solution 1 mg/ml was lower than that reported in adults and adolescents with rupatadine tablets (13,26), and almost no adverse reactions were reported with an incidence higher than 1%. Of note, the incidence of treatment-related somnolence, an important consideration from the viewpoint of reduced academic performance in school children, was very low (1.1% in the rupatadine group) and markedly lower than that observed in adults (13,26). This finding is also consistent with the low incidence of sedation generally reported for secondgeneration antihistamines in the paediatric population (7, 12, 17-20, 22, 24, 25). ...
Article
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Allergic rhinitis (AR) is one of the most common chronic diseases in childhood. No large, multicentre clinical trials in children with persistent allergic rhinitis (PER) have previously been performed. Rupatadine, a newer second-generation antihistamine, effective and safe in adults, is a promising treatment for children with AR. The aim of the present study was to evaluate the efficacy and safety of a new rupatadine oral solution in children aged 6–11 yr with PER. A multicenter, randomized, double-blind, placebo-controlled study was carried out worldwide. Patients between 6 and 11 yr with a diagnosis of PER according to ARIA criteria were randomized to receive either rupatadine oral solution (1 mg/ml) or placebo over 6 wk. The primary efficacy end-point was the change from baseline of the total nasal symptoms score (T4SS) after 4 wk of treatment. A total of 360 patients were randomized to rupatadine (n = 180) or placebo (n = 180) treatment. Rupatadine showed statistically significant differences vs. placebo for the T4SS reduction both at 4 (−2.5 ± 1.9 vs. −3.1 ± 2.1; p = 0.018) and 6 wk (−2.7 ± 1.9 vs. −3.3 ± 2.1; p = 0.048). Rupatadine also showed a statistically better improvement in the children's quality of life compared with placebo. Adverse reactions were rare and non-serious in both treatment groups. No QTc or laboratory test abnormalities were reported. Rupatadine oral solution (1 mg/ml) was significantly more effective than placebo in reducing nasal symptoms at 4 and 6 wk and was well tolerated overall. This is the first large clinical report on the efficacy of an H1 receptor antagonist in children with PER in both symptoms and quality of life.
... After administration of a single oral dose in adults, rupatadine is rapidly absorbed with a time to maximum concentration (T max ) of 0.75-1 h and a maximum concentration (C max ) of 2.3 ng/ml. The rapid absorption of rupatadine correlates with the onset of antihistaminic and anti-PAF activity as assessed by wheal and flare inhibition (22,(44)(45)(46). ...
... It is metabolized mainly by the cytochrome P450 enzyme 3A4 (CYP3A4), and some of its metabolites retain antihistaminic, but not anti-PAF, activity; the active metabolites contribute to its long duration of action (22). Elimination half-life (t 1/2 ) of 4.6 h after a single dose and 5.8 h after multiple once-daily administrations of rupatadine has been reported (46). ...
Article
In a review of rupatadine published in 2008, the primary focus was on its role as an antihistamine, with a thorough evaluation of its pharmacology and interaction with histamine H1 -receptors. At the time, however, evidence was already emerging of a broader mechanism of action for rupatadine involving other mediators implicated in the inflammatory cascade. Over the past few years, the role of platelet-activating factor (PAF) as a potent mediator involved in the hypersensitivity-type allergic reaction has gained greater recognition. Rupatadine has dual affinity for histamine H1 -receptors and PAF receptors. In view of the Allergic Rhinitis and its Impact on Asthma group's call for oral antihistamines to exhibit additive anti-allergic/anti-inflammatory properties, further exploration of rupatadine's anti-PAF effects was a logical step forward. New studies have demonstrated that rupatadine inhibits PAF effects in nasal airways and produces a greater reduction in nasal symptoms than levocetirizine. A meta-analysis involving more than 2500 patients has consolidated the clinical evidence for rupatadine in allergic rhinoconjunctivitis in adults and children (level of evidence Ia, recommendation A). Other recent advances include observational studies of rupatadine in everyday clinical practice situations and approval of a new formulation (1 mg/ml oral solution) for use in children. In this reappraisal, we revisit some key properties and pivotal clinical studies of rupatadine and examine new clinical data in more detail including studies that measured health-related quality of life and studies that investigated the efficacy and safety of rupatadine in other indications such as acquired cold urticaria, mosquito bite allergy and mastocytosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
... After administration of a single oral dose in adults, rupatadine is rapidly absorbed with a time to maximum concentration (T max ) of 0.75-1 h and a maximum concentration (C max ) of 2.3 ng/ml. The rapid absorption of rupatadine correlates with the onset of antihistaminic and anti-PAF activity as assessed by wheal and flare inhibition (22,(44)(45)(46). ...
... It is metabolized mainly by the cytochrome P450 enzyme 3A4 (CYP3A4), and some of its metabolites retain antihistaminic, but not anti-PAF, activity; the active metabolites contribute to its long duration of action (22). Elimination half-life (t 1/2 ) of 4.6 h after a single dose and 5.8 h after multiple once-daily administrations of rupatadine has been reported (46). ...
... Rupatadine exhibits a safety profile in children similar to that of other secondgeneration antihistamines such as cetirizine, levocetirizine, desloratadine or fexofenadine (22)(23)(24)(25) and was generally well tolerated. The overall incidence of adverse events in children aged 6-11 yr treated with rupatadine paediatric oral solution 1 mg/ml was lower than that reported in adults and adolescents with rupatadine tablets (13,26), and almost no adverse reactions were reported with an incidence higher than 1%. Of note, the incidence of treatment-related somnolence, an important consideration from the viewpoint of reduced academic performance in school children, was very low (1.1% in the rupatadine group) and markedly lower than that observed in adults (13,26). ...
... The overall incidence of adverse events in children aged 6-11 yr treated with rupatadine paediatric oral solution 1 mg/ml was lower than that reported in adults and adolescents with rupatadine tablets (13,26), and almost no adverse reactions were reported with an incidence higher than 1%. Of note, the incidence of treatment-related somnolence, an important consideration from the viewpoint of reduced academic performance in school children, was very low (1.1% in the rupatadine group) and markedly lower than that observed in adults (13,26). This finding is also consistent with the low incidence of sedation generally reported for secondgeneration antihistamines in the paediatric population (7, 12, 17-20, 22, 24, 25). ...
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Background & objectives: This randomized, double-blind clinical trial assessed the efficacy and safety of rupatadine 10 mg administered once-daily for 4 weeks compared with placebo and ebastine 10 mg in the management of symptoms of perennial allergic rhinitis (PAR). Methods: We randomly assigned 223 patients to receive placebo (n = 73), ebastine 10 mg (n = 79) or rupatadine 10 mg (n = 71). The efficacy and safety population analysis included 219 patients. The efficacy assessment was based on patients reflective assessment of the severity of symptoms in a diary card. Symptoms of allergic rhinitis included rhinorrhea, sneezing, nasal itching, nasal obstruction and ocular itching. The main variable of efficacy was the percentage of days where the score of the most severe symptom was less than or equal to one (Pdmax1). Furthermore, the change from baseline in the severity of total symptom score (5TSS) and nasal symptom score (4TNSS) were measured, as well as investigators and patients global assessment of efficacy. Results: Pdmax1 was nonsignificantly lower for rupatadine 10 mg (49%) and ebastine 10 mg (51%) than for placebo (42%) at the end of the study period. Both 5TSS and 4TNSS were significantly improved for rupatadine 10 mg users compared with placebo (p = 0.019 and p = 0.025, respectively). No significant differences were seen between active treatments. All treatments were similarly safe and well tolerated, with headache (33%) and somnolence (17%) as the most often reported adverse events in all treatment groups. Conclusions: Symptomatic relief of PAR symptoms with rupatadine 10 mg was rapidly and effectively attained. A 4-week treatment of patients suffering from PAR with rupatadine 10 mg is as effective and well tolerated as ebastine 10 mg.
... Promising H 1 -antihistamine/glucocorticoid nasal formulations are being investigated. [23][24][25][26][27][28] H 1 -antihistamines act as inverse agonists that combine with and stabilize the inactive conformation of the H 1 -receptor, shifting the equilibrium toward the inactive state. For more than 50 years, they were described as H 1 -receptor antagonists or H 1 -receptor blockers; however, these out-of-date terms do not accurately reflect their molecular mechanism of action ( Fig 2). ...
... In the future, H 1 -antihistamines will continue to be a cornerstone of pharmacologic treatment in patients with allergic rhinitis, allergic conjunctivitis, and urticaria. Novel agents, such as rupatadine, an H 1 -antihistamine/anti-platelet-activating factor agent, 23,24,66,71,123,125 might play a unique role. H 3 -antihistamines lead to an increase in norepinephrine and might have an advantageous decongestant effect in patients with allergic rhinitis administered with or without H 1 -antihistamines. ...
Article
In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future.
... After administration of a single oral dose in adults, rupatadine is rapidly absorbed with a time to maximum concentration (T max ) of 0.75-1 h and a maximum concentration (C max ) of 2.3 ng/ml. The rapid absorption of rupatadine correlates with the onset of anti-H 1 and anti-PAF activity as assessed by wheal and flare inhibition [25,[40][41][42]. ...
... An elimination half-life (t 1/2 ) of 5.8 h after multiple once-daily rupatadine administration has been reported [42][43][44]. In children, body weight-adjusted doses (2.5 mg for 10-25 kg children or 5 mg for >25 kg children) provided a similar exposure to rupatadine as that previously reported in pharmacokinetic studies in adults and adolescents (aged 12 years and older) [45]. ...
Article
Introduction: Rupatadine is a second-generation H1-antihistamine with dual affinity for histamine H1 and PAF receptors. Rupatadine is indicated for the treatment of allergic rhinitis and urticaria. Areas covered: A Medline search was conducted to identify preclinical and clinical studies of rupatadine. This was supplemented with additional articles obtained from online sources. The focus of this review is on the safety profile of rupatadine. Expert opinion: The review of these data indicates that rupatadine is highly selective for histamine H1-receptors, exhibits additional PAF antagonism in in vitro and in vivo studies, does not cross the blood-brain barrier, and has similar adverse events comparable with other second-generation antihistamines. Rupatadine is a safe and well tolerated drug in patients over 2 years old, with no central nervous system or cardiovascular effects and it can be taken with or without foods.
... [16] Studies of rupatadine, a novel antihistamine approved recently in 22 European countries for the treatment of seasonal AR (SAR), perennial AR (PAR) and chronic idiopathic urticaria in patients aged ‡12 years, have demonstrated that this agent has dual activity as both a histamine H 1 -and PAF-receptor antagonist. [12,17] Clinical trials have indicated that rupatadine 10 or 20 mg/day is significantly more effective than placebo and equally as effective as loratadine, desloratadine, cetirizine or ebastine in improving the symptoms of AR in patients with SAR, PAR and persistent AR (PER) and improves the health-related quality of life to a greater extent than placebo and to a similar extent as cetirizine over a period of 12 weeks in patients with PER. [12,17] Moreover, rupatadine has also been shown to be equally well tolerated as the comparator antihistamines, and additionally does not show any evidence of cardiotoxicity at doses up to ten times the recommended therapeutic dose of 10 mg/day. ...
... [12,17] Clinical trials have indicated that rupatadine 10 or 20 mg/day is significantly more effective than placebo and equally as effective as loratadine, desloratadine, cetirizine or ebastine in improving the symptoms of AR in patients with SAR, PAR and persistent AR (PER) and improves the health-related quality of life to a greater extent than placebo and to a similar extent as cetirizine over a period of 12 weeks in patients with PER. [12,17] Moreover, rupatadine has also been shown to be equally well tolerated as the comparator antihistamines, and additionally does not show any evidence of cardiotoxicity at doses up to ten times the recommended therapeutic dose of 10 mg/day. [18] This is especially important because life-threatening cardiac adverse effects such as prolongation of the QT interval and the development of torsades de pointes, a potentially fatal ventricular arrhythmia, have been associated with some second-generation antihistamines, notably terfenadine and astemizole. ...
Article
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Background: Rupatadine (Rupafin), a novel antihistamine approved recently in Europe for the treatment of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged>or=12 years, has been shown to be highly efficacious, and as safe and well tolerated as other commonly employed antihistamines in the treatment of allergic disease. There are, however, few data on the long-term safety of these antihistamines derived in accordance with the clinical safety recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA) and the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline. Objective: To assess the safety and tolerability of treatment with rupatadine 10 mg/day for 12 months in subjects with persistent AR (PER). Methods: A multicentre, open-label, phase IV study in patients recruited from 33 centres in Spain, from September 2002 to November 2005. The study enrolled 324 male and female patients (aged 12-70 years) with a medical history of PER for at least 12 months and a documented positive skin-prick test to an appropriate allergen. On 4 of the 7 days prior to start of treatment, the patients were required to have a minimum total nasal symptom score (TNSS [for sneezing, rhinorrhoea, nasal obstruction/congestion and nasal itching]) of >or=5. Of the 324 eligible patients starting treatment, 120 needed to be treated for more than 6 months and were followed up until the end of 12 months. All patients received rupatadine 10 mg/day and were allowed to continue their normal concomitant medication for all conditions, other than rhinitis, for up to 6 or 12 months. Safety was assessed by means of adverse events (AEs) reported by patients or detected by investigators, scheduled centralized ECG with special attention to Bazzet corrected QT interval (QTcB) and standard laboratory investigations. Results: Assessment of treatment compliance rates indicated 90% and 83% of patients to be compliant during the 1-6 months and 1-12 months treatment periods, respectively, with compliance rates>80% being associated with the majority of the study population reporting at least one AE. Overall, 74.1% and 65.8% of the patients reported at least one AE during the 1-6 months and 1-12 months treatment periods, respectively, compared with 20.4% and 10.8% of patients reporting at least one treatment-related AE during these periods. Disorders of the nervous system and respiratory thoracic and mediastinal system, in particular headache, somnolence and catarrh, were the three most common AEs reported by >5% of the patients during both treatment periods. Detailed ECG assessments demonstrated no clinically relevant abnormal ECG findings, nor any QTcB increases >60 msec or QTcB values>470 msec for any patient at any time during treatment. Serious AEs were reported in seven patients, of whom six were considered as unlikely to be related to rupatadine treatment, whereas one involving increased blood enzyme levels was considered as possibly related to rupatadine treatment. Conclusion: This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER.
... PAF causes vasodilatation and an increase in vascular permeability that may contribute to the appearance of rhinorrhea and nasal congestion. [7,8] PAF and histamine are known to complement each other in vivo; histamine is a mediator of early response, being released from preformed reservoirs in mast cells, whereas PAF is mainly synthesized de novo. [3] Results from other studies indicate that CC chemokines, including monocyte chemotactic protein (MCP)-1, MCP-3, RANTES (Regulated on Activation, Normal T-cell Expressed and Secreted), and eotaxin, may play an important role in inducing the selective recruitment of eosinophils and basophils to the allergic infl ammatory site. ...
... It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. [8,11,12] Though individually olopatadine and rupatadine are effi cacious in AR, additional pharmacodynamic activities of these drugs found in some studies indicate a likelihood of differences between these two drugs. The unique effect of rupatadine on interleukins (IL-6, IL-8) and olopatadine on leucotrienes (LTs), tromboxane A2 (TXA2), tachykinin, CC chemokines, leucocyte function-associated antigen 1 (LFA-1) expression has prompted us to design the present study. ...
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To compare the efficacy and safety of olopatadine and rupatadine in seasonal allergic rhinitis (SAR). A 2-week, single-centered, randomized, open, parallel group comparative clinical study was conducted on patients with SAR. Following inclusion and exclusion criteria, 70 patients were recruited and were randomized to two treatment groups and received the respective drugs for 2 weeks. At follow-up, clinical improvement was assessed in terms of change in total and differential count of leucocytes, serum Immunoglobulin E (IgE) level, Total Nasal Symptom Score (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scoring. Both the drugs significantly reduced the differential count (P<0.001) and absolute eosinophil count (P<0.001), but olopatadine was found to be superior. In olopatadine group, there was significantly higher reduction in serum IgE (P=0.01), TNSS (P<0.001) and RQLQ score (P=0.015) than that of rupatadine. Incidence of adverse effects was found to be less in olopatadine group when compared with rupatadine group. Olopatadine is a better choice in SAR in comparison to rupatadine due to its better efficacy and safety profile.
... Most antihistamines demonstrate a peak effect approximately 5 to 7 hours after oral administration, and the duration varies depending on the half-life of parent compound and active metabolites. 4 The aim of this study was to examine the efficacy of rupatadine, a new antihistamine H1 and PAF antagonist, [5][6][7] which provides effective symptom relief throughout the 24-hour dosing interval in patients with perennial AR (PAR). ...
... Previous studies with rupatadine showed a fast onset of action, 6 due to the fact that peak serum levels were reached around 0.5 to 1 hour after dosing. 7 This was the principal reason that morning dosing was scheduled in our patients. In spite of this fact, we expected to observe the most relief in morning symptoms in comparison with evening symptoms. ...
Article
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A circadian rhythm of symptoms has been reported in allergic rhinitis (AR). Severity of all major symptoms of AR, including runny nose, sneezing, and nasal congestion, is typically at its peak in the morning. The objective of this study was to explore the efficacy of the antihistamine and platelet activating factor (PAF) antagonist rupatadine in the morning and evening and to evaluate whether rupatadine provides effective symptom relief throughout the 24-hour dosing interval. A total of 308 patients ≥18 years of age with PAR was randomly assigned to once-daily rupatadine 10 mg, rupatadine 20 mg, or cetirizine 10 mg for 4 weeks in a placebo-controlled, double-blind study. The main outcome was the morning/evening reflective total symptom score (5TSS) over the treatment period. Secondary endpoints included morning/evening reflective nasal total symptom score (4NTSS), individual symptoms, Pdmax1 as percentage of days with daily severest symptom score ≤1, and subject/investigator evaluation of therapeutic response. All active groups were significantly more effective than placebo in improving morning and evening evaluations of 5TSS (P < 0.001) and 4NTSS (P < 0.001) at 2 or 4 weeks. At morning evaluation, there was a significant reduction from baseline for 5TSS with rupatadine 10 mg (-36.8%, P < 0.01) and 20 mg (-46.3%, P < 0.01) compared with placebo. Similarly, 4NTSS was reduced significantly more with rupatadine 10 mg (-34%, P < 0.05) and 20 mg (-41%, P < 0.01) compared with placebo. In the cetirizine 10 mg group, the reduction was -32.7% and -32.2% for 5TSS and 4NTSS, respectively, but this reduction was not significant compared with placebo. The percentage reduction was greater at evening than at morning evaluation. 5TSS reduction with rupatadine 10 mg (-40.7%, P < 0.05) and 20 mg (-49.9%, P < 0.01) and cetirizine 10 mg (-40.1%, P < 0.05) was significantly better than with placebo. 4NTSS values for active groups were also significantly improved versus placebo. When individual symptoms were assessed, statistically significant differences for rhinorrhea (P < 0.01), nasal itching (P < 0.01), and sneezing (P < 0.01) were shown in all active groups compared with placebo at morning and evening evaluations. Pdmax1 index was significantly improved for all active groups and the overall efficacy assessed by patients or investigators showed a significant improvement (P < 0.01) versus placebo at 2 and 4 weeks. The incidence of somnolence was significantly greater in all active groups versus placebo. The sustained 24-hour action of rupatadine 10 mg provides an effective control of morning and evening symptoms in patients with PAR treated for up to 4 weeks.
... Rupatadine (RT) is a non-sedating and selective histamine H1- receptor antagonist and platelet-activating factor inhibitor [1][2][3], which is safe and effective for the treatment of allergic rhinitis and chronic urticaria [3][4][5][6][7]. It is extensively metabolized by P450 3A4 [2,8], and the major metabolites of RT are desloratadine (DT) and 3-hydroxydesloratadine (3-OH-DT), which are active and con- tribute to the overall efficacy of the drug [4,9,10]. ...
... Rupatadine (RT) is a non-sedating and selective histamine H1- receptor antagonist and platelet-activating factor inhibitor [1][2][3], which is safe and effective for the treatment of allergic rhinitis and chronic urticaria [3][4][5][6][7]. It is extensively metabolized by P450 3A4 [2,8], and the major metabolites of RT are desloratadine (DT) and 3-hydroxydesloratadine (3-OH-DT), which are active and con- tribute to the overall efficacy of the drug [4,9,10]. It is essential to evaluate the potential effect of the main metabolites and their back-conversion to the parent drug during analysis. ...
... For example, cetirizine is a metabolite of hydroxyzine, levocetirizine is the active R-enantiomer of cetirizine, desloratadine is a metabolite of loratadine, and fexofenadine is a metabolite of terfenadine. New H 1 antihistamines continue to be developed and introduced for clinical use 51,52 ; however, such medications should be scrutinized closely because they may or may not represent important clinically relevant advances when compared with existing second-generation medications in the class. To date, no second-generation H 1 antihistamine appears to have superior overall efficacy to the others, although some are safer than others. ...
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In this review, we compare and contrast the clinical pharmacology, efficacy, and safety of first-generation H1 antihistamines and second-generation H1 antihistamines. First-generation H1 antihistamines cross the blood-brain barrier, and in usual doses, they potentially cause sedation and impair cognitive function and psychomotor performance. These medications, some of which have been in use for more than 6 decades, have never been optimally investigated. Second-generation H1 antihistamines such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine cross the blood-brain barrier to a significantly smaller extent than their predecessors. The clinical pharmacology, efficacy, and safety of these medications have been extensively studied. They are therefore the H1 antihistamines of choice in the treatment of allergic rhinitis, allergic conjunctivitis, and urticaria. In the future, clinically advantageous H1 antihistamines developed with the aid of molecular techniques might be available.
... Rupatadine is a new second-generation H 1 -antihistamine, with an additional anti-platelet activating factor effect, that is approved and marketed for the treatment of AR and urticaria in adults and adolescents (aged ≥12 years) [8]. Rupatadine has been shown to be effective in the treatment of seasonal, perennial and persistent AR [9][10][11], with a fast onset of action [12] and a very good long-term safety profi le [13]. ...
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According to current guidelines, new second-generation oral Hi-antihistamines, as well as intranasal corticosteroids (ICSs), are recommended for the treatment of allergic rhinitis (AR) in adults and children. To assess changes in AR severity, in addition to nasal symptoms and health-related quality of life (HRQoL), after 4 weeks of treatment with rupatadine in a cohort of AR patients. A subanalysis of a longitudinal, observational, prospective, multicenter Spanish study was carried out in spring-summer 2007. Enrolled patients had a clinical diagnosis of AR of at least 2 years' evolution, a total nasal symptom score (TNSS) of at least 5, and had not received antihistamines in the previous week or ICSs in the previous 2 weeks. HRQoL (ESPRINT-15 questionnaire), disease severity (using both the original and modified Allergic Rhinitis and its Impact on Asthma [ARIA] classifications), and nasal symptoms (TNSS) were measured at baseline and after 4 weeks of rupatadine treatment. Data from a cohort of 360 patients treated with rupatadine were analyzed (57.2% women, 42.5% with intermittent AR, 36.4% with asthma, and 61.7% with conjunctivitis). After 4 weeks of treatment, the patients showed a significantly lower mean (SD) TNSS (8.2 [1.9] vs 3.1 [2.1], P < .001), a significant improvement in HRQoL (3.0 [1.2] vs 1.0 [0.9], P < .001) and significantly reduced AR severity (P < .0001). In addition to an improvement in nasal symptoms and HRQoL, rupatadine reduced AR severity after 4 weeks of treatment.
... Candidate drug in this study, rupatadine, is marketed as fumarate under brand name Rupafin ® 10 mg film coated tablets [5], indicated for symptomatic treatment of allergic rhinitis, urticaria in adults and adolescents over 12 years of age [6] with recommended dosing is 10 mg once per day as a single dose [1]. ...
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Background: Rupatadine is an antihistaminic drug that is used for the treatment of allergic rhinitis, chronic idiopathic urticarial, additionally, it can be used as safe and effective alternative to loratadine. Aim: Development of bio-analytical method for rapid quantification of rupatadine in human plasma and its clinical application in bioequivalence study of generic and reference products of rupatadine 10mg film coated tablet. Methods: Extracted rupatadine was chromatographed with mobile phase of methanol: 0.5% formic acid 80:20 v/v at flow rate 0.5ml/min, ESI positive mode, and m/z 416282.1, 383337 for rupatadine and loratadine as internal standard respectively. The bioequivalence study was conducted in a crossover design invovlving 24 volunteers and pharmacokinetic parameters AUC 0-t, AUC 0-inf, Cmax, and Tmax were used for assessment of bioequivalence of the two products. Results: The average recovery of rupatadine from human plasma was 87.567%, limit of quantitation was 0.01ng/ml, and the cor- relation coefficient (r2) obtained was 0.9997. Statistical analysis for the pharmacokinetic parameters using ANOVA test showed a non- significant difference between generic and reference products included in the study. Conclusion: The developed bioanalytical LC/MS/MS method is simple, sensitive, precise, accurate and valid for rupatadine quanti- fication in human plasma and is suitable for application in pharmacokinetic and bioavailability studies and therapeutic monitoring of rupatadine in management of allergic disease to ensure effective therapeutic drug levels and avoid potential undesired adverse events. Results of bioavailability study showed that both generic and reference products are bioequivalent and both products can be considered interchangeable in medical practice. Keywords: Rupatadine; Bioanalytical Method Validation; LC/MS/MS; Non-Sedating Antihistamine; Allergic Rhinitis
... Rupatidine is a combined H1 and PAF antagonist [7], licensed in several parts of the world for treating allergic rhinitis and for chronic urticaria, but it is not clear what (if anything) its action on PAF receptors adds to its therapeutic efficacy over and above its antihistamine action [8]. The withdrawal from the market of another less-sedating antihistamine, terfenadine, ushered in the modern era of regulatory concern over cardiac safety of non-cardiac drugs. ...
... Rupatadine is a sgAH of the piperidine subfamily which differs from other sgAHs in its ability to also block PAF receptors. 92,93 The recommended dosage of rupatadine is 10 mg once a day. Studies in vitro showed that rupatadine blocks hERG channels with a IC50 of 8100 nM. ...
Article
The symptoms of chronic urticaria, be it chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CindU), are mediated primarily by the actions of histamine on H1‐receptors located on endothelial cells (the wheal) and on sensory nerves (neurogenic flare and pruritus). Thus, 2nd generation H1‐antihistamines (sgAHs) are the primary treatment of these conditions. However, many patients are poorly responsive to licensed doses of antihistamines. In these patients, the current EAACI/GA2LEN/EDF/WAO guideline for urticaria suggests updosing of sgAHs up to 4‐fold. However, such updosing is off label and the responsibility resides with the prescribing physician. Therefore, the safety of the drug when used above its licensed dose is of paramount importance. An important aspect of safety is potential cardiotoxicity. This problem was initially identified some 20 years ago with cardiotoxic deaths occurring with astemizole and terfenadine, two early sgAHs. In this review we discuss the mechanisms and assessments of potential cardiotoxity of H1‐antihistamines when updosed to four‐times their licensed dose. In particular, we have focused on the potential of H1‐antihistamines to block hERG (human Ether‐a‐go‐go‐Related Gene) voltage‐gated K+ channels, also known as Kv11.1 channels according to the IUPHAR classification. Blockade of these channels causes QT prolongation leading to torsade de pointes that may possibly degenerate into ventricular fibrillation and sudden death. We considered in detail bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, loratadine, desloratadine, mizolastine and rupatadine and conclude that all these drugs have an excellent safety profile with no evidence of cardiotoxicity even when updosed up to four times their standard licensed dose, provided that the prescribers carefully consider and rule out potential risk factors for cardiotoxicity, such as the presence of inherited long QT syndrome, older age, cardiovascular disorders, hypokalemia and hypomagnesemia, or the use of drugs that either have direct QT prolonging effects or inhibit sgAH metabolism.
... and platelet activating factor antagonist56. This combined effect may provide a special advantage in the current treatment of patients with seasonal and perennial allergic rhinitis78, and the drug has recently been administered in persistent allergic rhinitis [9]. Our main objective was to evaluate the reduction in delayed nasal obstruction as measured by acoustic rhinometry in patients treated with rupatadine after a nasal allergen challenge, and to determine nasal NO (nNO) values in a group of asymptomatic allergic patients. ...
Article
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To measure the reduction in nasal obstruction using acoustic rhinometry in patients with allergic rhinitis treated with rupatadine. We performed a randomized, double-blind, cross-over, placebo-controlled clinical trial in asymptomatic patients with allergic rhinitis. Patients received rupatadine 10 mg or placebo once daily for 3 days, in 2 subsequent periods separated by a washout interval of 14 days. We performed a nasal allergen challenge during each period, and measured nasal volume using acoustic rhinometry and nasal nitric oxide (nNO) at baseline, and at 2 hours and 24 hours after the challenge. We also evaluated nasal symptoms (rhinorrhea, itching, obstruction, and sneezing), as well as total symptom score (T4SS) at the same time points as for the primary objective. The study population comprised 30 outpatients with a mean (SD) age of 28 (10) years. Nasal airway blockage was significantly lower in the rupatadine group than in the placebo group (47%, P < .05) at 2 hours postchallenge. nNO in the rupatadine-treated patients remained unaltered, unlike in the placebo-treated group, where levels decreased at 2 hours. After treatment with rupatadine, patients showed a lower decrease in the mean total symptoms score at 2 hours (3.6 [2.6]) compared with placebo (3.9 [2.9]), although these differences did not achieve statistical significance. Overall, rupatadine was well tolerated and no serious or unexpected adverse events were observed. Rupatadine 10 mg can reduce nasal obstruction assessed by objective measures and is well tolerated in patients with allergic rhinitis.
... According to the authors, rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis and chronic urticaria. So far, no adverse cardiovascular effects where observed in preclinical or extensive clinical testing, or negative significant effects on cognition or psychomotor performance (including a practical driving study) (76)(77)(78). There is no drug interaction with azithromycin, fluoxetine and lorazepam, but it should not be administered with known CYP3A4 inhibitors (78). ...
Article
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Urticaria is a disorder characterized by rapid onset of localized swelling of the skin or mucosa, called wheals or urtica. According to frequency and duration, urticaria can be divided into acute and chronic type. Chronic urticaria is any type of urticaria occurring every day or twice per week, lasting longer than 6 weeks. Chronic urticaria is a common disorder and estimated prevalence is 1% of the population. Also, it is not rare in childhood. The pathogenesis of chronic urticaria has not yet been completely understood. Chronic urticaria is a heterogeneous group of disorders, and according to the etiology and cause, several groups of chronic urticaria are distinguished, i.e. autoimmune, pseudoallergic, infection-related, physical urticaria, vasculitis urticaria and idiopathic urticaria. Treatment and management of chronic urticaria can be non-pharmacological and pharmacological, and sometimes it is not possible to control the disease with antihistamines only, which are considered to be the mainstay of treatment. In severe cases of chronic urticaria, especially if autoimmunity has been proven, several authors describe different modules of immunomodulation: cyclosporine, cyclophosphamide, mycophenolate-mofetil, omalizumab, plasmapheresis, systemic corticosteroids, and immunoglobulin therapy. This article primarily addresses the treatment of chronic idiopathic and autoimmune urticaria.
... In the case of 3-hydroxydesloratadine, initial hydroxylation is followed by Phase II conjugation with glucuronic acid. 2 Azithromycin is a semisynthetic macrolide antibiotic chemically related to erythromycin and clarithromycin. Several clinically significant interactions have been identified since the approval of erythromycin, usually related to the inhibition of the CYP enzyme systems. ...
Article
Rupatadine is an oral active antihistamine and platelet-activating factor antagonist indicated for the management of allergic rhinitis and chronic urticaria in Europe. The purpose of this study was to describe the effect of the concomitant administration of azithromycin and rupatadine on the pharmacokinetics of rupatadine and its metabolites after repeated doses. This was a multiple-dose, randomized, open-label, 2-way, crossover, Phase I study in which healthy male and female volunteers received rupatadine 10 mg once a day for 6 days either alone or with azithromycin 500 mg on day 2 and 250 mg from day 3 to day 6. Treatments were administered after a fasting period of 10 hours with 240 mL of water, and fasting conditions were kept until 3 hours postmedication. A washout period of at least 21 days between the 2 active periods was observed. Blood samples were collected and plasma concentrations of rupatadine and its metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examination, electrocardiograms, and laboratory screen controls at baseline and the final study visit. Twenty-four healthy volunteers (15 males, 9 females; mean [SD] age, 25.67 [5.58] years; weight, 65.96 [8.57] kg) completed the study. Except for maximum observed concentration during a dosing interval (Cmax,ss) of 3-hydroxydesloratadine, on average, there were no statistically significant differences in mean plasma concentrations in any of the main pharmacokinetic parameters of rupatadine, desloratadine, and 3-hydroxydesloratadine when administered in combination with azithromycin or alone. The Cmax,ss ratio was 111 (90% CI, 91-136) and area under the plasma concentration-time curve during a dosing interval (AUC0-tau) ratio had a value of 103 (90% CI, 91-117). The corresponding ratios for the rupatadine metabolites were 109 (90% CI, 100-120) for Cmax,ss and 103 (90% CI, 96-110) for AUC0-tau for desloratadine and 109 (90% CI, 103-115) for Cmax,ss and 104 (90% CI, 100-108) for AUC0-tau for 3-hydroxydesloratadine. Point estimates for Cmax,ss ratios using paired data were 111% for rupatadine, 109% for desloratadine, and 109% for 3-hydroxydesloratadine. The 90% CIs were included in the interval 80% to 125% for desloratadine and 3-hydroxydesloratadine, whereas 90% CI for rupatadine was shifted to the right of the interval used for comparing bioavailability of the drugs. A total of 5 subjects reported 9 AEs; 5 of these were thought to be related to the drug administration and all were categorized as mild or moderate. The reported AEs were somnolence (1/24 in the rupatadine group and 1/24 in the rupatadine plus azithromycin group), diarrhea (1/24 in the rupatadine plus azithromycin group), and gastric discomfort (2/24 in the rupatadine plus azithromycin group). Four AEs were considered not to be related (2 episodes of headache, 1 anemia, 1 cheilitis). All were resolved spontaneously. No serious AEs were reported. The results of this study in these healthy volunteers found no significant differences in pharmacokinetic parameters other than Cmax,ss of 3-hydroxydesloratadine between rupatadine 10 mg administered alone or with azithromycin 500 mg on day 2 and 250 mg from day 3 to day 6. The administration of rupatadine compared with rupatadine plus azithromycin met the regulatory definition of bioequivalence in terms of exposure and rate parameters; however, Cmax,ss of rupatadine was outside the conventional confidence interval.
... PAF receptor antagonists are not routinely available, but rupatadine, a novel compound with both H1 antihistamine and PAF receptor antagonistic effects, has been shown to have efficacy in allergic disorders, including allergic rhinitis. 210 ...
Article
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Atopic dermatitis (AD) is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10%-20% of infants and 1%-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. At least half of the children with AD develop some other form of atopic disease later in life. The pathogenesis of AD involves a complex interplay of factors, including genetic predisposition due to altered immune or skin barrier function, interactions with the environment, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of AD in human and animal model systems. These insights provide new therapeutic potential for the treatment of human AD.
... In addition, the higher H 1 receptor selectivity of second generation molecules has been considered a major pharmacological advantage over older first generation molecules, which also displayed significant serotoninergic-, muscarinic-, and R 2adrenergic-blocking abilities; moreover, newer congeners such as rupatadine have been developed, showing antagonistic properties at both H 1 -and platelet-activating factor (PAF) receptors (8), possibly leading to improved symptomatic control because of the simultaneous antagonism of two crucial mediators of the allergic response. Altogether, such a pharmacodynamic and pharmacokinetic profile characterizing second generation antihistamines bears an obvious clinical advantage in the therapy of allergic diseases; although the sedative effects of older antihistamines are still of great clinical value under specific circumstances (i.e., in children or agitated patients, during cancer chemotherapy, or during surgical procedures where sedation is desirable), second generation molecules have nowadays become a first choice for the treatment of many symptoms (including rhinorrhea, contraction of bronchial and gastrointestinal smooth muscle, and many forms of itch) associated with allergic diseases such as allergic rhinitis, chronic urticaria, and atopic dermatitis. ...
Article
Drug-induced arrhythmias, particularly those caused by a prolonged QT interval, have become a critical safety issue for compound selection during development by pharmaceutical companies and for health care regulators. The last two decades have witnessed enormous progress in the definition of the clinical conditions that facilitate the occurrence of such serious adverse effects, of its molecular basis, and in the preclinical strategies aimed at early identification of the cardiotoxic liability of compounds undergoing investigation or already used in the clinic. Moreover, despite the fact that acquired factors play an obvious role in drug-induced arrhythmias, it has become evident that the disease is often manifested upon the interaction of strong environmental stressors with specific genetic determinants of the affected individuals; in that sense, few examples can illustrate the existing interaction between acquired and genetic factors in disease manifestation better than drug-induced arrhythmogenesis. Progress in this field has been mainly driven by a strong interaction among various disciplines, including medicinal chemistry, pharmacology, electrophysiology, molecular genetics, and clinical cardiology; such an interdisciplinary approach has often generated unexpected discoveries of great clinical value, allowing clinicians to drive drug selection toward compounds of proven efficacy and safety. Historically, studies on antihistamines have paved the way for much of our current understanding of the mechanisms and problems associated with QT prolongation and drug-induced arrhythmogenesis; therefore, in this perspective, we will attempt to summarize how basic research studies have helped the interpretation of clinically relevant phenomena (from basics to clinics...) and how this information has prompted new emphasis in preclinical studies aimed at predicting the cardiotoxic potential of compounds (...and back). The current availability of several strategies provided with great predictive potential, together with an increased awareness of physicians, pharmaceutical industries, and health care regulators to this potentially serious cardiovascular side effect, has significantly decreased the risk associated with drug-induced arrhythmias caused by drugs newly introduced into the market; nevertheless, given the large number of cases of QT prolongation still occurring during treatment with a wide variety of congeners, it seems appropriate to review the issue of the cardiotoxic actions of antihistamines, as a better comprehension of the underlying mechanisms and risk factors is likely to contribute to the improvement of the risk/benefit ratio for pharmacological treatment in several therapeutic areas.
... Uriach & Co, SA, Barcelona, Spain) is a new molecule with dual-affinity binding for both histamine H 1 and PAF receptors, with anti-inflammatory properties as well. [15][16][17] The pharmacologic parameters of rupatadine 18 and the safety profile at high doses were reviewed in detail previously. 19 -21 Rupatadine is indicated for the treatment of allergic rhinitis 22 and chronic urticaria. ...
Article
Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor. To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU. A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment. Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.
... 10 Rupatadine is well known as a dual blocker of histamine H1 and PAF-receptors, by means of a variety of experimental and clinical studies which provide scientific evidence that this can be an effective and well tolerated treatment for AR and urticaria. 11,12 The objective of the current study was to compare the efficacy and safety of rupatadine 10 mg versus a very well known second generation H1 antihistamine such as desloratadine 5 mg, and to also compare the efficacy and safety of both drugs versus placebo, all administered once daily, in the treatment of SAR over a 4-week period. This will provide the first clinical evidence of a direct comparison between both types of H1-receptor antagonists. ...
Article
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H1-antihistamines are recommended as the first-line symptomatic treatment of allergic rhinitis. The objective of this study was to evaluate the effects of rupatadine (RUP) versus desloratadine (DES) in subjects with seasonal allergic rhinitis (SAR). To assess the efficacy and safety of RUP in SAR in comparison with placebo (PL) and DES. A randomized, double-blind, multicenter, international, and PL-controlled study was carried out. The main selection criteria included SAR patients over 12 years old with a positive prick test to a relevant seasonal allergen for the geographic area. Symptomatic patients at screening with a nasal symptom sum score of ≥6 points (nasal discharge, nasal obstruction, sneezing, and nasal pruritus), a non-nasal score of ≥3 points (ocular pruritus, ocular redness, and tearing eyes), and a rhinorrhea score of ≥2 points with laboratory test results and electrocardiography within acceptable limits were included in the study. Change from baseline in the total symptom-score (T7SS) over the 4-week treatment period (reflective evaluation) was considered the primary efficacy variable. Secondary efficacy measures included total nasal symptom score (T4NSS) and conjunctival symptom score (T3NNSS), both of which are reflective and instantaneous evaluations. Furthermore questions related to quality of life (eg, sleep disturbances or impairment of daily activities) have also been evaluated. Safety was assessed according to adverse events reported, as well as laboratory and electrocardiography controls. A total of 379 patients were randomized, of which 356 were included and allocated to PL (n = 122), RUP (n = 117), or DES (n = 117). Mean change of T7SS over the 4-week treatment period was significantly reduced in the RUP (-46.1%, = 0.03) and DES (-48.9%, = 0.01) groups, compared with PL. Similarly, RUP and DES were comparable and significantly superior to PL for all secondary endpoints, including nasal and conjunctival symptoms and patients' and investigator's overall clinical opinions. Symptom score evaluation (both reflective and instantaneous evaluations) throughout the treatment period showed a progressive and maintained significant improvement with both treatments at day 7 ( = 0.01), day 14 ( = 0.007), and day 21 ( = 0.01) in comparison with PL. Adverse events were scarce and were similar in both treatment groups. Electrocardiography (QTc) and lab test results did not show any relevant findings. RUP is a very good choice for SAR due to its contribution to the improvement of nasal (including obstruction) and non-nasal symptoms to a similar degree as DES.
... However, these e ects are not related to interaction with speci c H1 receptors and, as such, are not histamine-speci c [8,51]. e cardiac safety of rupatadine has been extensively and repeatedly investigated in clinical studies [4,45,52]. ...
Article
Rupatadine is a modern non-sedating H1-antihistamine that also haswith additional antagonist effects on platelet-activating factor (PAF). Under the tradenames Rupafin® and Urtimed®, Rrupatadine is approvedregistered in Germany for the treatment of allergic rhinitis and urticaria infor adults and children aged over 12 years. In this review, the available literature available to date onregarding the pharmacological profile and clinical application of Rrupatadine is reviewed and compared to other conventional histamines. In conclusionFinally, the side effects, safety and interaction profileincompatibility of Rrupatadine are discussed. Due to CYP p450 metabolism, Rrupatadine should not be given together with Eerythromycin, Kketoconazole or grapefruit juice. Rupatadine has been found to be effective and safe Iin a variety of randomized clinical trials both in both seasonal and perennial allergic rhinitis, as well as inbut also chronic urticaria Rupatadine has been found as effective and safe.
... These molecules inhibit both PAF actions and 5-lipoxygenase, as LDP-392 [61], or thromboxane synthase [62], or iNOS induction [63]. Rupatadine, as well, is both an oral PAFR antagonist and a histamine H(1)receptor antagonist [64]. ...
Article
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In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors.
... Rupatadine PK parameters in Japanese subjects are shown to be in close agreement with the results exhibited by several white studies [24][25][26]. Similarly to the linear increase observed in white studies with single doses of 10-40 mg rupatadine [14], dose proportionality analysis in this study revealed that the estimated slope values for C max, AUC 0-1 and AUC 0-τ after single and repeated doses of rupatadine supports linearity. The 90% CI of the slope (β) for log transformed C max and AUC 0-τ values for the metabolite UR-12788 did not fulfil the criteria of dose proportionality on Day 5. ...
Article
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Introduction: Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses. Methods: In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS). Results: Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment-emergent adverse events (TEAEs) in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests. Conclusions: This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.
... Дезлоратадин -это первичный активный метаболит лоратадина, селективного блокатора Н 1 -гистаминовых рецепторов II поколения. Дезлоратадин обладает сходными фармакодинамическими свойствами, однако по активности превосходит другие препараты этой группы в 2,5-4 раза [21,22]. Многочисленные исследования свидетельствуют о том, что наличие антигистаминного, противоаллергического и противовоспалительного эффекта, высокая селективность и аффинность к H 1 -гистаминовым рецепторам определяют высокую эффективность дезлоратадина при АР, в частности в отношении заложенности носа, ринореи, зуда глаз, неба, чихания и слезотечения. ...
Article
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I и II поколения. Подчеркиваются преимущества неседативных антигистаминных препаратов II поколения, в особенности т. н. активных метаболитов (фексофенадин, цетиризин, левоцетиризин, дезлоратадин). Подробно представлены данные по лоратадину и дезлоратадину как по одним из наиболее эффективных препаратов у детей с аллергическим ринитом. Обсуждаются возможные направления исследований по обеспечению эффектив-ного контроля аллергического воспаления у детей, резистентных к лекарственным препаратам. Ключевые слова: аллергический ринит у детей, антигистаминные препараты, лоратадин, дезлоратадин. (Вопросы современной педиатрии. 2013; 12 (6): 67–72) This literature review contains analysis of research results on treatment of allergic rhinitis in children according to the evidence-based medicine. Oral and intranasal antihistamine drugs along with intranasal steroids are the first-line drugs for treatment of allergic rhinitis, although the latter are more efficient in suppression of nasal stuffiness. First-and second-generation antihistamine agents used nowadays in medical practice are discussed in the article. The advantages of non-sedative 2d-genereation antihistamine drugs, especially so called active metabolites (fexofenadine, cetirizine, levocetirizine, desloratadine) are emphasized. The data on loratadine and desloratadine as ones of the most effective drugs in childhood allergic rhinitis are shown in detail. The possible directions for the further investigations in order to provide effective control over allergic inflammation in children resistant to medicinal agents are discussed.
... Powoduje to synergistyczne działanie dwóch mechanizmów. Ma to ogromne znaczenie, gdyż liczne badania potwierdziły, że histamina nie jest jedynym mediatorem zaangażowanym w kaskadzie reakcji alergicznej, a PAF odgrywa istotną rolę w procesie zapalnym, co potwierdziły badania in vivo i in vitro [46][47][48][49][50] . PAF uwalniany jest z różnych komórek, w tym komórek śródbłonka, neutrofili, makrofagów lub komórek tucznych, co powoduje aktywację chemotaksji lub uwolnienie mediatorów zapalenia z komórek posiadających receptory dla PAF (neutrofile, eozynofile, mastocyty, płytki krwi). ...
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... PAF uwalniany jest z różnych komórek, w tym komórek śródbłonka, neutrofili, makrofagów lub komórek tucznych, co powoduje aktywację chemotaksji lub uwolnienie mediatorów zapalenia z komórek posiadających receptory dla PAF (neutrofile, eozynofile, mastocyty, płytki krwi). Jego istotną rolę w procesie zapalenia alergicznego oraz w patofizjologii alergicznego nieżytu nosa i astmy potwierdziły badania in vivo i in vitro [34][35][36][37] . To powoduje wyjątkową skuteczność Rupatadyny zwłaszcza w przewlekłym alergicznym nieżycie nosa (PANN). ...
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Introduction: Rupatadine fumarate is a second-generation antihistamine provided with a potent, long-lasting and balanced in vivo dual platelet-activating factor (PAF) and histamine antagonist activity and it uniquely combines both activities at a high level of potency. Rupatadine has a rapid onset of action and a long-lasting effect, so a once-daily dosing is permitted, moreover is well tolerated by young adults and the elders. Rupatadine does not present the side effects of first-generation H1-antihistamines, such as somnolence, fatigue, headache, impaired memory and learning, sedation, increased appetite, dry mouth, dry eyes, visual disturbances, constipation, urinary retention and erectile dysfunction. Areas covered: This study evaluates the effectiveness and safety of rupatadine in chronic urticaria (CU) and acquired cold urticaria (ACU), through a systematic review of the literature. Expert opinion: Patients affected by urticaria are often discouraged because frequently their disease does not recognize a cause and it is unresponsive to treatments. Patients can control their symptoms assuming second-generation H1-antihistamines, such as rupatadine. Several randomized, double-blind, placebo-controlled trials testify effectiveness and safety of rupatadine in CU and ACU. However, further clinical trials to evaluate the efficacy of rupatadine in different urticaria subtypes and to test the safety of doses higher than 20 mg are encouraged.
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With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment. To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period. A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) >or=45, nasal obstruction score <or=12, and overall assessment of PER >or=2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS. In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo (n = 185), cetirizine (n = 175) and rupatadine (n = 183). Rupatadine (P = 0.008) but not cetirizine (P = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P = 0.013; cetirizine vs placebo, P = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated. Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.
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Rupatadine (UR-12592, 8-chloro-6, 11-dihydro-11-[1-[(5-methyl3-pyridinyl) methyl]-4-piperidinylidene]-5H-benzo[5,6]-cyclohepta[1,2b]pyridine ) is a novel compound that inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors (Ki(app) values against [3H]WEB-2086 binding to rabbit platelet membranes and [3H]-pyrilamine binding to guinea pig cerebellum membranes were 0.55 and 0.10 microM, respectively). Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation. Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's duration of action was long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modified spontaneous motor activity nor prolonged barbiturate-sleeping time in mice, which indicates a lack of sedative effects. Overall, rupatadine combines histamine and PAF antagonist activities in vivo with high potency, the antihistamine properties being similar to or higher than those of loratadine, whereas rupatadine's PAF antagonist effects were near those of WEB-2066. Rupatadine is therefore a good candidate for further development in the treatment of allergic and inflammatory conditions in which both PAF and histamine are implicated.
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To review the efficacy and safety of first- and newer-generation antihistamines for the management of allergic rhinitis and chronic idiopathic urticaria (CIU), with a focus on management in the pharmacy. A literature review was performed using MEDLINE (1966-October 2005), with no time or language restrictions. Key words or phrases used were histamine, antihistamine(s), first- and second-generation, allergic rhinitis, chronic idiopathic urticaria, quality of life, impairment, sedation, cost-effectiveness, astemizole, cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine, hydroxyzine, ketotifen, and mizolastine. Additional references were found in the bibliographies of the articles cited. Clinical trials and other experimental studies of the use of antihistamines for the management of allergic rhinitis and CIU were selected. Review papers and guidelines were also included. First-generation antihistamines are effective at ameliorating the symptoms of allergic rhinitis and CIU; however, they are associated with adverse effects due to a lack of selectivity for the histamine H(1)-receptor and an ability to bind to cerebral H(1)-receptors. Newer-generation agents, in general, possess high H(1)-receptor selectivity and a low tendency to cross the blood-brain barrier, while maintaining efficacy. In general, safety at elevated doses has been demonstrated for the newer antihistamines, although higher rates of sedation and impairment have been reported with increasing doses for some agents. Pharmacists can play an important role in the management of allergic rhinitis and CIU by considering the relative advantages of newer-generation agents when reviewing treatment options.
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A simple practical questionnaire technique for routine clinical use, the Dermatology Life Quality Index (DLQI) is described. One hundred and twenty patients with different skin diseases were asked about the impact of their disease and its treatment on their lives; a questionnaire, the DLQI, was developed based on their answers. The DLQI was then completed by 200 consecutive new patients attending a dermatology clinic. This study confirmed that atopic eczema, psoriasis and generalized pruritus have a greater impact on quality of life than acne, basal cell carcinomas and viral warts. The DLQI was also completed by 100 healthy volunteers; their mean score was very low (1.6%, s.d. 3.5) compared with the mean score for the dermatology patients (24.2%, s.d. 20.9). The reliability of the DLQI was examined in 53 patients using a 1 week test-retest method and reliability was found to be high (gamma s = 0.99).
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The effects of rupatadine, a new dual antagonist of both histamine H1 and platelet-activating factor receptors, were studied on human cloned hKv1.5 channels expressed in Ltk− cells using the whole-cell patch-clamp technique. Rupatadine produced a use- and concentration-dependent block of hKv1.5 channels (KD=2.4±0.7 μM) and slowed the deactivation of the tail currents, thus inducing the ‘crossover’ phenomenon. Rupatadine-induced block was voltage-dependent increasing in the voltage range for channel opening suggesting an open channel interaction. At potentials positive to +10 mV the blockade decreased with a shallow voltage-dependence. Moreover, rupatadine also modified the voltage-dependence of hKv1.5 channel activation, which exhibited two components, the midpoint of the steeper component averaging −25.2±2.7 mV. When the intracellular K+ concentration ([K+]i) was lowered to 25% the voltage-dependent unblock observed at positive potentials was suppressed and the activation curve in the presence of rupatadine did not exhibit two components even when the midpoint of the activation curve was shifted to more negative potentials (−30.3±1.3 mV). On channels mutated on the residue R485 (R485Y) which is located on the external entryway of the pore the rupatadine-induced block did not decrease at potentials positive to +10 mV. In contrast, on V512M channels rupatadine reproduced all the features of the blockade observed on wild type channels. All these results suggest that rupatadine blocks hKv1.5 channels binding to an external and to an internal binding site but only at concentrations much higher than therapeutic plasma levels in man. Efflux of K+ promotes the unbinding from the external site. Furthermore, rupatadine binds to an internal site and dramatically modifies the voltage-dependence of channel opening. British Journal of Pharmacology (1999) 128, 1071–1081; doi:10.1038/sj.bjp.0702890
Article
Allergic rhinitis (AR) is a common disease in many developed countries. Its prevalence is estimated at ≈10–20% of the general population Understanding the pathogenesis and mechanisms that lead to allergic nasal disease and, thus, to the symptomatology of allergic rhinitis provides a framework for a rational therapy in this disorder. Treatment has to focus primarily on the symptomatology of the patient, taking into account the time, duration and severity of the disease. In the position paper on the treatment of allergic rhinitis of the European Academy of Allergology and Clinical Immunology, 1 guidelines to treat seasonal and perennial allergic rhinitis are presented. Table 1 will help to make a rational choice.
Article
To examine the inhibitory potential of rupatadine, a new H1-antihistamine and anti-PAF agent, on histamine and TNF-alpha release. Comparison with an H1-antihistamine (loratadine) and a PAF-antagonist (SR-27417A). Dispersed canine skin mast cells were used to assess the effect of the drugs tested on FcepsilonRI-dependent and -independent histamine release; the human HMC-1 cell line was used to study TNF-alpha release. Before stimulation mast cell populations were treated with increasing concentrations of rupatadine, loratadine and SR-27417A. Histamine and TNF-alpha release were measured following 15-30 min and 3 h activation, respectively. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF-alpha release with IC50 2.0+/-0.9 microM, 2.1+/-1.1 M and 4.3+/-0.6 microM, respectively. Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF-alpha release, whereas SR-27417A only exhibited inhibitory effect against TNF-alpha.
Article
Allergic rhinitis (AR) is a global health concern and shares a high comorbidity with asthma. Recent research suggests that different allergic diseases, such as AR, asthma, allergic conjunctivitis and chronic idiopathic urticaria (CIU), are evoked by common pathological mechanisms characterised by the release of histamine and other inflammatory mediators. Although H(1) receptor antagonists are the mainstay of therapy for allergic disease, the unacceptably high incidence of anticholinergic and CNS-related side effects of first-generation H(1) antagonists led to the search for improved second-generation H(1) antagonists. While many of these agents were largely devoid of CNS side effects, their tendency for drug-drug interactions (e.g., terfenadine and astemizole) resulted in an increased incidence of cardiotoxicity. Furthermore, second-generation H(1) antagonists exhibited weak anti-inflammatory properties and had no effect on nasal congestion. These observations emphasised the need for newer anti-allergic agents with a broader spectrum of activity and an improved safety profile. Among the newer H(1) antagonists currently in clinical development, desloratadine and mizolastine are the most widely studied. Both have a rapid onset of action, and desloratadine has demonstrated clinical efficacy in AR, CIU and seasonal asthma. Desloratadine has several advantages over other H(1) antagonists in that it has proven decongestant activity, a sparing effect on the use of bronchodilators (beta(2)-agonists) and a low potential for drug interactions. The broad anti-inflammatory properties of desloratadine and mizolastine, which distinguish these agents from other H(1) antagonists in clinical development (e.g., norastemizole and levocetirizine), suggest they may have a more profound impact on the underlying disease in patients suffering from different forms of allergy. The lack of clinical efficacy and safety data on rupatadine and HSR-609, both novel H(1) antagonists, precludes an accurate assessment of their potential for treating allergic disease. Epinastine and efletirizine are being developed exclusively for topical application and are unlikely to play a significant role in the management of allergic diseases as a whole.
Article
Rupatadine is a new agent for the management of diseases with allergic inflammatory conditions, such as seasonal and perennial rhinitis. The pharmacological profile of rupatadine offers particular benefits in terms of a strong antagonist activity towards both histamine H1 receptors and platelet-activating factor (PAF) receptors. Rupatadine has a rapid onset of action, and its long-lasting effect (>24 h) permits once-daily dosing. Rupatadine should not be used in combination with the cytochrome P450 inhibitors, such as erythromycin or ketoconazole, due to an increase in AUC and Cmax for rupatadine, although no clinically relevant adverse events have been reported. In addition, rupatadine, at the recommended dose of 10 mg, has been shown to be free of sedative effects and not to cause significant changes in the corrected QT interval in special populations, including the elderly, nor when coadministered with erythromycin or ketoconazole. Preclinical data have also shown that rupatadine and its main active metabolites did not interfere with cloned human HERG channel and did not affect in vitro isolated dog Purkinje fibers at concentrations at least 2000 times greater than those obtained with therapeutic doses in humans. Rupatadine is clinically effective in relieving symptoms in patients with seasonal and perennial allergic rhinitis. Newly published data on its efficacy and safety suggest that this compound may improve the nasal and non-nasal symptoms in comparison to other currently available second generation H1 receptor antihistamines.
Article
The aim of this study is to establish the efficacy and safety of rupatadine vs ebastine and placebo in the treatment of seasonal allergic rhinitis (SAR). Rupatadine is a new second generation H(1)-antihistamine with once-daily dosing that may provide better control of symptoms than the currently used H(1)-receptor blockers because of its dual pharmacological profile (anti-PAF and anti-H(1)). In a multicentre study, 250 patients with SAR were included in a double-blind, randomized, parallel-group and placebo-controlled study. Patients received either rupatadine 10 mg, ebastine 10 mg or placebo once daily for 2 weeks. The main efficacy outcome was based on the patient's record of severity of nasal symptoms (sneezing, nasal itching, runny nose and nasal obstruction) and nonnasal symptoms (conjunctival itching, tearing and pharyngeal itching). The daily total symptom score (DTSS) was the mean of the DSS recorded for each of the seven symptoms assessed, and the mean DTSS (mDTSS) was the mean of the DTSS values for each study day. Significant differences in mDTSS were detected between rupatadine and placebo (33% lower for rupatadine group; P = 0.005) after 2 weeks of treatment. The TSS for rupatadine were 22% lower than for ebastine, although the differences were not statistically significant. No serious adverse events were reported during the study period. Rupatadine 10 mg once daily was clearly superior to placebo in alleviating the symptoms of SAR over a 2-week period. In comparison with ebastine, rupatadine shows a trend towards a better profile as regard several secondary efficacy variables.
Article
Chronic idiopathic urticaria (CIU) can have a profound effect on patient quality of life (QOL). Ideally, any therapy used to treat CIU should be effective across a wide range of doses without causing unwanted side effects; a wide therapeutic window allows the physician to tailor treatment to the individual. Oral H1 antihistamines are the mainstay of therapy for CIU, but agents within this class diverge in their individual therapeutic indices. The literature was reviewed to compare the currently available oral H1 antihistamines regarding their efficacy and safety at a wide range of doses. If sedation and cognitive impairment are considered relevant to treatment selection due to their effect on QOL and safety, then newer-generation agents should be selected over older-generation antihistamines. There are few well-controlled clinical studies in which newer-generation agents have been directly compared. Moreover, there are no evidence-based data demonstrating statistical superiority of one newer-generation agent over another in the treatment of CIU. However, of the newer agents, those that are labelled nonsedating at recommended doses (fexofenadine, loratadine, and desloratadine) should be selected over cetirizine. In cases where the physician judges that a higher-than-recommended dose should be prescribed, or when the patient is likely to take a higher dose, the relative safety profile of these agents demands detailed consideration.
Article
This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).
Article
Rupatadine is a novel compound with potent dual antihistamine and platelet-activating factor antagonist activities and no sedative effects. To evaluate the efficacy of rupatadine, 10 mg once daily, and placebo on allergen-induced symptoms (including nasal congestion), nasal airflow, nasal secretion, and subjective tolerability in response to grass pollen in a controlled allergen-exposure chamber. In a randomized, double-blind, placebo-controlled, crossover trial, 45 patients with a history of seasonal allergic rhinitis received rupatadine or placebo every morning for 8 days in 2 different periods separated by a 14-day washout interval. On day 8 of each crossover period, patients underwent a 6-hour allergen exposure in the Vienna Challenge Chamber, where a constant and homogeneous concentration of aeroallergens was maintained. Subjective and objective assessments were performed online during the exposure. Subjective single and composite nasal and nonnasal symptoms were consistently less severe with rupatadine use than with placebo use starting from the first evaluation at 15 minutes to the end of the 6-hour Vienna Challenge Chamber challenge, with the most significant effects seen for nasal rhinorrhea, nasal itching, sneezing attacks, and total nasal symptoms (P < .001 for all). All the other symptoms (including nasal congestion, P < or = .005) were also significantly reduced with active treatment compared with placebo use. Mean secretion weights and overall feeling of complaint were significantly lower with rupatadine therapy than with placebo use (P < or = .001). Overall, rupatadine treatment was well tolerated. Rupatadine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to aeroallergens in a controlled exposure chamber.
Article
Urticaria is dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major preformed mediator histamine produces a prototypic, short-lived urticaria. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig)E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgE-bound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50% of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment.
Article
The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.
Article
Sleep is fundamental for physical and mental health as well as daytime performance and represents a crucial aspect in the personal representations of well-being. Sleep disturbances in patients with chronic disorders constitute a factor that contributes to exacerbate symptoms, complicate management, and affect mood and quality of life (QoL). Allergic diseases are a global health problem of increasing prevalence that affects up to 15% of the population in Western countries. Sleep problems associated with allergic diseases may play a role in worsening the burden of illness, contributing to impairment of the QoL. The aim of this review was to describe the most common causes leading to sleep disturbance in allergic patients and their consequences on the QoL. The possible negative effects of treatment on sleep parameters has been also considered.
Article
Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with a strong antagonist activity towards both histamine H(1) receptors and platelet-activating factor receptors. The use of rupatadine is indicated in adult and adolescent patients (> 12 years of age) suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment of these diseases, rupatadine is at least as effective as ebastine, cetirizine, loratadine and desloratadine. A very good safety profile of rupatadine has been evidenced in various studies, including a long-term (1-year) safety study. Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors.
Article
Allergic rhinitis (AR) and perennial nonallergic rhinitis (PNAR) represent conditions affecting millions of individuals across the world. Although the diagnosis of AR might be presumptively based on the types of symptoms and the history of allergen triggers, confirmation requires documentation of specific IgE reactivity. In contrast, PNAR is a condition with similar symptomatology but in which the patient has no identifiable specific allergic sensitivities. This review presents the diverse options of currently available pharmacologic agents for the treatment of AR and PNAR, including intranasal corticosteroids, H1-antihistamines, decongestants, cromolyn sodium, antileukotrienes, anticholinergics, capsaicin, anti-IgE, and intranasal saline. Furthermore, appropriate stepped-up, stepped-down pharmacotherapeutic algorithms are described for the various forms of rhinitis.