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Background: A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited., Objective: We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods., Methods: In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845., Results: The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period., Conclusions: We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

To gain a comprehensive overview of the landscape of clinical trials for the H 1 -receptor antagonists (H 1 R antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, H 1 R antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of H 1 R antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of H 1 R antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future., (© 2023. The Author(s).)

Inflammatory Bowel Disease (IBD) is an autoimmune condition with complicated pathology and diverse clinical signs. TNFα is believed to play a crucial role in the pathogenesis of IBD. We recently identified fexofenadine, a well-known antagonist of histamine H1 receptor, as a novel inhibitor of TNFα signaling. Additionally, cytosolic phospholipase A2 (cPLA2) was isolated as a binding target of fexofenadine, and fexofenadine-mediated anti-TNF activity relied on cPLA2 in vitro. The objective of this study is to determine whether fexofenadine is therapeutic against chemically-induced murine IBD model and whether cPLA2 and/or histamine H1 receptor is important for fexofenadine's anti-inflammatory activity in vivo by leveraging various genetically modified mice and chemically induced murine IBD models. Both dextran sulfate sodium- and 2, 4, 6-trinitrobenzene sulfonic acid-induced murine IBD models revealed that orally delivered fexofenadine was therapeutic against IBD, evidenced by mitigated clinical symptoms, decreased secretions of the proinflammatory cytokine IL-6 and IL-1β, lowered intestinal inflammation, and reduced p-p65 and p-IĸBα. Intriguingly, Fexofenadine-mediated protective effects against IBD were lost in cPLA2 deficient mice but not in histamine H1 receptor-deficient mice. Collectively, these findings demonstrate the therapeutic effects of over-the-counter drug Fexofenadine in treating DSS-induced IBD murine and provide first in vivo evidence showing that cPLA2 is required for fexofenadine's therapeutic effects in murine IBD model and probably other inflammatory and autoimmune diseases as well.

Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of anti-leishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient's immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 μM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Objective: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX)., Methods: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups., Results: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group., Conclusion: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes eventually leads to the recurrence and metastasis of tumours. Thus, the development of therapeutic strategies based on the mechanisms by which cells acquire resistance to prolong their survival rate in chemotherapy drug treatment failure patients are warranted. In this study, we found that the resistant cells acquired increased migratory and invasive capabilities, and this transformation was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway deregulation in the resistant cells. Finally, we reported for the first time that terfenadine augmented the effect of epirubicin (EPI) better than Taxol and cisplatin (DDP) by inhibiting migration, invasion, and the EMT phenotype, and the combination therapy also reversed Notch signalling pathway and enhanced the accumulation of fluorescent P-gp substrate rhodamine 123 (Rh123). Similar activities of terfenadine on EPI were observed in xenografts. All of our results confirmed that terfenadine combined with EPI synergistically inhibits the growth and metastatic processes of resistant cells both in vitro and in vivo. Therefore, terfenadine or its derivatives are a promising approach for the clinical challenge of resistance in patients with advanced NSCLC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. This paper compares peripheral blood mononuclear cell (PBMC) incubation with FXF and osthole, by studying FXF, osthole and histamine cytokine secretion in PBMC in vitro cultures. Mabtech kits determined the interleukins IL-1β, IL-4, IL-10, IL-13 and TNF-α. The influence of the above active substances on cytokine secretion in PBMC's and serum was assessed: cytokines were IL-1β, IL-4, IL-10, IL-13 and TNF-α; and cytokine levels secreted by untreated PBMCs in pure culture medium formed the absolute control (ctrl). We determined that osthole affects PBMC cytokine secretion to almost precisely the same extent as FXF (IL-1β, IL-4, IL-10 and TNF). In addition osthole had greater IL-13 blocking ability than FXF. Moreover, we observed significantly decreased IL-4 level in histamine/osthole theatment compared to histamine alone. Meanwhile, FXF not significantly decrease the level of IL-4 increased by histamine. This data indicates osthole's strong role in allergic inflamation. All results confirm our hypothesis that osthole is a natural histamine antagonist and therefore can be beneficially used in antihistamine treatment of conditions such as allergies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To observe the effect of combined therapy on seasonal allergic rhinitis(AR) and quality of life. Method: Ninety-six patients with severe seasonal AR unresponsive to intranasal corticosteroids alone were divided randomly into nasal budesonide group(group A),Nasal Budesonide combined with fexofenadine hydrochloride group(group B),and budesonide combined with montelukast group(group C).The symptom scores,Uni-VAS,and rhinoconjunctivitis quality of life(RQLQ) were evaluated 2 and 4 weeks after treatment initiation. Result: In the group B and C,the symptom scores,Uni-VAS,and RQLQ were significantly lower than the group A( P <0.05).As for nasal itching(after 2 weeks),rhinorrhea and sneezing,the symptom scores and Uni-VAS of group B were significantly lower than that of group C( P <0.05).However,compared to group B,the improvement of nasal obstruction in group C was much better( P <0.05).There was no significant difference in other symptoms and RQLQ. Conclusion: For patientswith severe seasonal AR unresponsive to intranasal corticosteroids alone,combined therapy can help alleviate clinical symptoms and improve quality of life.The combination of drugs should be individulized based on the severity of symptoms., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.

The aim of this study was to evaluate the effect of fexofenadine on intestinal inflammation. HCT116 and COLO205 cells were pretreated with fexofenadine and then stimulated with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 expression was determined by real-time reverse-transcription polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. DNA-binding activity of nuclear factor-κB was assessed by electrophoretic mobility shift assay. The molecular markers of endoplasmic reticulum (ER) stress were evaluated by Western blot analysis and PCR. In the acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days with or without fexofenadine. IL-10(-/-) mice were used to evaluate the effect of fexofenadine on chronic colitis. Fexofenadine significantly inhibited the upregulated expression of IL-8 in HCT116 and COLO205 cells stimulated with TNF-α. Fexofenadine suppressed nuclear factor-κB DNA-binding activity. C/EBP homologous protein mRNA expression was enhanced in the presence of TNF-α, and it was dampened by pretreatment of fexofenadine. In addition, the induction of ER stress markers caspase-12 and p-eukaryotic initiation factor 2 (eIF2)-α was significantly suppressed by the pretreatment of fexofenadine. Administration of fexofenadine significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IκB kinase activation was significantly decreased in fexofenadine-pretreated mice. Finally, fexofenadine significantly reduced the severity of colitis and the immunoreactivity of caspase-12 and p-eIF2-α in IL-10(-/-) mice as compared with controls. These results suggest that fexofenadine is a potential therapeutic agent for the treatment of inflammatory bowel disease., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Olopatadine is one of the second-generation H1 antihistamines that were used for treating allergic disorders initially in Asia, and now also in Western countries. Whereas several trials compared the efficacy on chronic urticaria among second-generation H1 antihistamines, no study has directly compared the clinical efficacy between olopatadine and other H1 antihistamines in patients with chronic idiopathic urticaria (CIU). In this study, we address this issue for the first time and conclude that olopatadine is a good candidate for the treatment of CIU., (© 2015 S. Karger AG, Basel.)

In this study, we report on the efficacy of combination therapy of second-generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis or pemphigoid nodularis patients, in whom conventional therapy was ineffective. All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice a day for 4 weeks in addition to other medications they had been taking. We assessed the manifestations of the lesions and itching intensity before and after the therapy, and we evaluated each patient as (i) markedly improved, (ii) improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients (13.3%) were evaluated as markedly improved, and the lesions of one patient completely disappeared. Three patients (20.0%) were evaluated as improved, and six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved by combination therapy of fexofenadine and montelukast, in which nine cases (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were involved. No patients revealed any side effects. This study revealed that combination therapy of fexofenadine and montelukast was effective for some patients with conventional therapy-resistant prurigo nodularis and pemphigoid nodularis., (© 2013 Wiley Periodicals, Inc.)

Objective: The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications, including the antiallergic drug fexofenadine. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the anti-allergic effect of fexofenadine among Jordanians., Materials and Methods: An assessment of the severity of allergic rhinitis symptoms was performed for all patients (n = 260) pre- and 7 days into fexofenadine. MDR1 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)., Results: Relative to baseline, fexofenadine treatment was associated with significant reduction in allergic individual and total scores (p < 0.0001). Male gender was associated with less mean reduction in total allergic rhinitis symptoms score than in female (p < 0.05). In multivariate analysis, male gender was negatively correlated with response to fexofenadine (p = 0.01). The MDR1 gene C1236T polymorphism showed significant correlation with changes in total symptoms score from baseline in males (p < 0.05) but not in females. No significant correlation between fexofenadine response parameters and G2677T or the C3435T polymorphism was observed., Conclusions: The MDR1 gene polymorphism C1236T was associated with the anti-allergic effect of fexofenadine among male Jordanians.

This randomized, double-blind, placebo-controlled crossover study compared inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30-90 min versus 2 h), shorter time to maximum effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were no clinically significant ethnic differences in responsiveness to the drugs.

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models., (© 2012 Blackwell Publishing Ltd.)

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain&#95;e.jsp).

Background: Clara cell 10-kD protein (CC10) is well known to be an immuno-suppressive protein secreted from airway epithelial cells after inflammatory stimulation and is involved in the development of allergic disorders. Although histamine H1 receptor antagonists are used for the treatment of allergic disorders, the influence of the agents on CC10 production is not well understood. In the present study, we examined the influence of a histamine H1 receptor antagonist, fexofenadine hydrochloride (FEX) on CC10 production in vitro and in vivo., Methods: Nasal epithelial cells (5 x 10(6) cells/ml) were stimulated with 20 ng/ml TNF-alpha in the presence of various concentrations of FEX for 24 hours. CC10 levels in culture supernatants were examined by ELISA. Patients with Japanese cedar pollinosis were treated orally with FEX twice a day at a single dose of 60 mg for two weeks during Japanese cedar pollen season (February 2011 to April 2011). CC10 levels in nasal secretions were also examined by ELISA., Results: The addition of FEX into cell cultures caused increase in CC10 production induced by TNF-alpha stimulation, and the minimum concentration that caused significant increase was 200 ng/ml. Oral administration of FEX also increased CC10 levels in nasal secretions from pollinosis patients along with attenuation of clinical symptoms., Conclusion: The ability of FEX to enhance CC10 production may account, at least in part, for the clinical efficacy of the agent in allergic disorders, including allergic rhinitis.

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients' quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

Background: In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP., Methods: In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16-85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph., Results: Initial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season., Conclusions: Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.

Background: Nasal H(3) receptors might have a role in mediating the effects of histamine in patients with allergic rhinitis., Objective: This study explored the effect of the potent oral H(3) receptor antagonist PF-03654746 in combination with an oral H(1) receptor antagonist on the objective (acoustic rhinometry) and subjective (symptoms) responses to nasal allergen challenge., Methods: Twenty patients with out-of-season allergic rhinitis displaying a 30% or greater decrease in minimum nasal cross-sectional area (A(min)) after bolus (ragweed) complete nasal allergen challenge at screening were studied by using a randomized, double-blind, single-dose, 4-way crossover design. Treatments included 10 mg of PF-03654746 plus 60 mg of fexofenadine (group 1), 1 mg of PF-03654746 plus 60 mg of fexofenadine (group 2), 60 mg of fexofenadine/120 mg of pseudoephedrine (group 3), and placebo (group 4). After dosing, subjects underwent complete nasal allergen challenge. Nasal symptom scores (no. of sneezes and 0- to 5-point scores for severity of congestion, itching, and rhinorrhea), A(min) (in square centimeters), and nasal volume (in cubic centimeters) were recorded 15, 30, 45, and 60 minutes after allergen. There was a minimum 10-day washout between periods., Results: The following symptom scores were significantly (P ≤ .05) reduced by active treatments versus placebo: group 1, congestion of -0.7 (SE, 0.3), itching of -1.0 (SE, 0.3), rhinorrhea of -1.3 (SE, 0.3), and sneeze of -8.8 (SE, 1.5); group 2, itching of -0.6 (SE, 0.3), rhinorrhea of -0.8 (SE, 0.3), and sneeze of -9.1 (SE, 1.5); and group 3, rhinorrhea of -0.7 (SE, 0.3) and sneeze of -7.0 (SE, 1.5). There was no significant effect of any treatment on mean A(min) proportion or nasal volume proportion after nasal allergen challenge., Conclusions: In combination with fexofenadine, single doses of PF-03654746 caused a reduction in allergen-induced nasal symptoms. H(3) receptor antagonism might be a novel therapeutic strategy to further explore in patients with allergic rhinitis., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Urticaria is mainly caused by mast cell-derived histamine through the histamine H(1) receptor. Antihistamines are occasionally used on demand upon a recurrence of urticaria; therefore, rapidly acting agents should be explored. The onset of action is assumed to depend on time to maximum concentration (T(max)), but the speed of action needs to be evaluated not only through blood concentration analysis but also by measuring in vivo effectiveness., Methods: In this study, we chose two representative second-generation antihistamines (bepotastine and fexofenadine) with relatively short T(max) values and evaluated their effects on histamine-induced skin responses using both visual and laser Doppler imaging scales., Results: Suppression of histamine-induced flare and itch was observed 3 and 6 h after administration of both antihistamines. Attenuation of itch was seen 30 min after the administration of each drug and thereafter until 6 h. In addition, bepotastine suppressed flare formation after only 30 min following application., Conclusion: These results suggest that antihistamines suppress histamine-induced itch and flare, followed by wheal formation, and that bepotastine suppresses skin symptoms sooner after administration than fexofenadine does, which is relatively consistent with the T(max) results., (Copyright © 2012 S. Karger AG, Basel.)

We recently showed that intranasal phototherapy represents an efficient therapeutic modality for the treatment of patients with seasonal allergic rhinitis (SAR). The aim of this pilot study was to compare the efficacy of intranasal phototherapy with that of the new generation antihistamine fexofenadine HCl in SAR. A randomized open study was conducted in patients with a history of moderate-to-severe ragweed-induced SAR. Thirty-one patients were randomly assigned to receive either intranasal irradiation three times a week for 2 weeks, or 180 mg fexofenadine HCl per day for 2 weeks. Each patient kept a diary of symptoms for nasal obstruction, nasal itching, rhinorrhea, sneezing and palate itching. Total nasal score (TNS), a sum of scores for nasal symptoms, was also calculated. In the rhinophototherapy group the individual scores significantly decreased compared with baseline for all of the parameters. In the fexofenadine HCl group none of the scores improved significantly at the end of the treatment except sneezing. TNS was significantly decreased in the rhinophototherapy group, but no significant change was observed in the fexofenadine HCl group after 2 weeks of treatment. In conclusion, we found that intranasal phototherapy is more efficient than fexofenadine HCl in reducing clinical symptoms for SAR., (© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.)

Rationale: Evidence-based medicine represents the effort to highlight the best intervention for patients, clinicians, and policy makers, each from their respective viewpoint, to solve a particular health condition. According to a recently diffused grading system of evidence and recommendations for medical interventions, efficacy and safety represent 2 of the most important features to consider, and data from meta-analyses of randomized controlled clinical trials (RCTs) is the strongest supporting demonstration. Fexofenadine has been used for its efficacy and safety in the treatment of allergic rhinitis (AR) for many years although no meta-analyses supporting its use currently exist. The aim of this study is to assess for the first time the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analytic analysis of existing RCTs. Since specific evidence should be provided to address recommendations in a pediatric population, the quality of the estimates of this subgroup analysis is assessed., Methods: All double-blind, placebo-controlled randomized trials assessing the efficacy of fexofenadine in AR were searched for in OVID, Medline, and Embase databases up to December 2007. Outcomes were extracted from original articles; when this information was not available, the authors of each trial were contacted. Some graphics were digitalized. The RevMan 5 program was used to perform the analysis. GradePro 3.2.2 was used to assess the quality of the evidence for a pediatric population., Results: Of 2,152 identified articles, 20 were potentially relevant trials. Eight studies satisfied the inclusion criteria and were included in the meta-analysis. The main reasons for exclusion were: unnatural exposure, strong study limitations, an atypical outcome measurement, a design for other outcomes, and not being a placebo-controlled, single-blind study. Seven trials investigated a mixed population of adults and children, 1 trial investigated only children, and 1 trial only adults. In 1,833 patients receiving fexofenadine (1,699 placebo), a significant reduction of the daily reflective total symptom scores (TSS) (SMD –0.42; 95% CI –0.49 to –0.35, p < 0.00001) was found. Positive results were also found for morning instantaneous TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and congestion). The safety analysis did not show a significant difference in reported adverse events (AE) between the active and placebo treatment groups (OR = 1.03; 95% CI 0.87–1.22, p = 0.75). A very low heterogeneity between the studies was detected, so a fixed-effects model was used. The mean quality level of the included trials was medium. Specific information for a pediatric population may be assumed with a moderate quality of evidence from only 1 study and with a low quality of evidence, mainly due to indirectness, from the others., Conclusions: This study has 5 major strengths: it represents the first attempt to evaluate the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analysis of RCTs; there was consistency between positive results in terms of efficacy in TSS and in individual symptoms; a large population was studied; there was an irrelevant interstudy heterogeneity, and the AE frequency was similar in both groups. All of these values encourage the recommendation of fexofenadine for AR. Further research focused on the benefits and disadvantages for a pediatric population is needed.

Objective and Design: This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis., Subjects and Methods: Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2., Results and Conclusions: Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

Drug-transporters play an important role in the disposition of clinical medicines. Although there are plural studies that have reported on the stereoselective pharmacokinetics related to cytochrome P450s, previous reports of the stereoselective pharmacokinetics related to drug-transporters including P-glycoprotein have been lacking. This article reviews the pharmacokinetic differences between fexofenadine enantiomers in humans and summarizes the previous reports that co-administration of P-glycoprotein inhibitors has altered the stereoselective pharmacokinetics of fexofenadine enantiomers. Both in vitro and in vivo studies have demonstrated that both itraconazole and verapamil are potent P-glycoprotein inhibitors. Therefore, by comparing the stereoselective pharmacokinetics of (R)- and (S)-fexofenadine with or without itraconazole and verapamil, the contribution of P-glycoprotein-mediated transport to fexofenadine stereoselective pharmacokinetics could be estimated. In our studies, the plasma concentrations of (R)-fexofenadine were greater than those of the corresponding (S)-enantiomer. Co-administration of itraconazole and/or verapamil significantly increased the AUC(0 - 24) of both enantiomers; their influence on the P-glycoprotein-mediated transport of (S)-fexofenadine was greater than that of the (R)-enantiomer. However, because t(max) and t(1/2) were constant in both studies, the fexofenadine stereoselective pharmacokinetics appears to be due to P-glycoprotein efflux activity in the small intestine, which suggests that P-glycoprotein probably possesses the chiral discriminatory abilities.

Objective: This study was designed to assess the hypothesis that leukotriene receptor antagonists (LTRAs) would provide additional symptom relief in asthmatic children with persistent AR already taking regular antihistamine. The effects of 16-week treatment of LTRA in addition to fexofenadine (FEX) on persistent AR in asthmatic children were examined., Study Design: Consecutive children with stable asthma and persistent AR were invited in this randomized, double-blind, placebo-controlled study. After a 2-week run-in period in which subjects were given FEX alone, they were randomly assigned to take LTRA or placebo in addition to FEX for 16 weeks, followed by 8 weeks of follow-up phase with FEX taken alone. Symptom scoring, rhinoscopy, acoustic rhinometry, spirometry, nasal secretion extraction and blood taking for IL-4 and IL-13 analysis were performed after a 2-week run-in and at the end of treatment., Results: Forty-four subjects with a median (IQR) age of 12.2 (10.1-14.1) years were recruited. At week 4 of treatment, the between-group differences in the mean changes of daytime sneezing score (mean difference (95% CI) = -0.35 (-0.59, -0.12), P = 0.004), nighttime sneezing score (mean difference (95% CI) = -0.37 (-0.62, -0.11), P = 0.007) and daytime composite score (mean difference (95% CI) = -1.08 (-1.92, -0.25), P = 0.013) were significant. Acoustic rhinometry also demonstrated a nearly significant difference in nasal volume change between groups at 16 weeks of treatment (mean difference (95% CI) = 0.572 (0.090-1.054), P = 0.021). IL-4 and IL-13 were not detected in the majority of nasal secretion or serum samples., Conclusions: Additional LTRA provided a more rapid relief on sneezing at the 4-week time point. This combination therapy also maintained a greater nasal volume and this might translate to lesser nasal congestion.

Background: Fexofenadine is one of several second-generation H(1)-antihistamines approved for the treatment of various allergic disorders; however, it shows numerous unique properties that make it an optimal choice for many patients., Objective: To review the pharmacology, efficacy and safety of fexofenadine and the attributes differentiating it from other H(1)-antihistamines., Methods: We performed a literature search in PubMed/MEDLINE (1966 - March 2009) using the keywords fexofenadine, antihistamine, allergic rhinitis and chronic urticaria. We also reviewed data provided by the manufacturer in addition to reports from various governmental agencies., Results/conclusions: Fexofenadine is devoid of sedative and anticholinergic effects and may offer equivalent or greater efficacy in treating allergic disorders compared with other currently available second-generation H(1)-antihistamines. In addition, fexofenadine may offer cost savings over other selected H(1)-antihistamines owing to its recent availability in generic form in the US.

The cytochrome P450 epoxygenase, CYP2J2, converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs). We found recently that this enzyme is dramatically up-regulated in a variety of established human carcinoma cell lines and in human cancerous tissue and promotes the neoplastic phenotype. In the present study, we tested the hypothesis that specific inhibitors of CYP2J2 related to the drug terfenadine are effective antitumor agents. Four of these inhibitors (compounds 4, 5, 11, and 26) were tested for effectiveness in vitro and in vivo. In Tca-8113 cells, the CYP2J2 inhibitors decreased EET production by approximately 60%, whereas they had no effect on CYP2J2 mRNA or protein expression. Compound 26 inhibited the proliferation of human tumor cells, reduced their ability to adhere, invade, and migrate, and attenuated activation of epithelial growth factor receptor signal and kinases and phosphatidylinositol 3 kinase/Akt pathways. Inhibition of CYP2J2 also significantly potentiated human tumor cell apoptosis and caused a corresponding increase in caspase-3 activity and change in expression of apoptosis-related proteins Bax and Bcl-2. In murine xenograft models using MDA-MB-435 cells, treatment with compound 26 significantly repressed tumor growth, decreased lung metastasis, and was associated with increased expression of the anticancer genes CD82 and nm23, without causing toxicity. These data suggest that CYP2J2 inhibitors hold significant promise for use in treatment of neoplastic diseases.

To study the effect of fexofenadine on extensive alopecia areata (AA), we evaluated retrospectively 121 patients with AA having alopecia in more than 50% of the scalp and followed them for at least 6 months. Patients were treated by immunotherapy using diphenylcyclopropenone or squaric acid dibutylester with or without oral fexofenadine. The regrowth score was estimated as decrease of Severity of Alopecia Tool (SALT) score. In AA with atopic background (atopic AA), the mean regrowth score of the fexofenadine group was 1.333 (n = 33) and that of the control 0.471 (n = 34). The fexofenadine group showed significantly better regrowth than control by Mann-Whitney's U-test (P = 0.00213). In non-atopic AA, the mean regrowth score of the fexofenadine group was 1.303 (n = 33) and that of the control 1.048 (n = 21). There was no significant difference by Mann-Whitney's U-test (P = 0.872). Together, fexofenadine is a helpful reagent in the treatment extensive atopic AA with contact immunotherapy.

In Japan, information on daily Japanese cedar pollen counts is made public during pollen season. If symptom severity and treatment outcome are predictable according to these pollen counts, management of seasonal allergic rhinitis may become more precise. The aims of the study were to evaluate the relationship between airborne pollen counts, symptom severity and treatment outcome in Japanese cedar pollinosis patients. In the randomized study, patients with moderate to most severe Japanese pollinosis were treated with fexofenadine (60 mg BD) or fexofenadine and nasal corticosteroids for 2 weeks. During the same period daily airborne pollen counts were measured. A total of 105 adult patients were enrolled. No difference of treatment efficacy was seen among groups. Detailed results of efficacy and safety were previously described elsewhere. In univariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study tended to affect symptom severity (P = 0.053) and the mean cumulative amount of airborne pollen during the treatment period tended to show difference among five treatment outcome categories (P = 0.066). In multivariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study was identified as the only significant factor of symptom severity (P = 0.0327) and cumulative amount of airborne pollen during the treatment period (P = 0.027) and allergic history (P = 0.027) were significant factors of treatment outcomes. No serious adverse effect was reported during the study. The amount of airborne pollen may be predictive of both symptom severity and treatment outcome.

Background: Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion., Objective: This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihistamines desloratadine, fexofenadine, and levocetirizine., Methods: MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levocetirizine for nasal congestion associated with AR were excluded., Results: Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetirizine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P < or = 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P < or = 0.005)., Conclusions: In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.

Background: Interleukin-16 (IL-16) is a cytokine that induces selective migration of CD4+ cells and participates in inflammatory diseases including allergic rhinitis. Histamine and prostaglandin D(2) are important chemical mediators of allergic inflammation, and antiallergic drugs are commonly used for the treatment of allergic rhinitis. It remains unknown whether treatment with the drugs affects IL-16., Objective: We evaluated the variability of IL-16 and the effects of the antiallergic drugs fexofenadine (40 mg/kg/day) and ramatroban (30 mg/kg/day) on IL-16 in an OVA-sensitized BALB/c murine experimental allergic rhinitis model., Methods: We measured the expression level of IL-16 protein in the mouse nasal septal mucosa by immunohistochemistry, and the serum level of IL-16 by ELISA. Several other parameters associated with allergic rhinitis (nasal symptoms, OVA-specific IgE, eosinophil and T cell infiltration) were also measured., Results: Local and systemic expressions of IL-16 were significantly increased in OVA-sensitized mice when compared to the nonsensitized group. Fexofenadine and ramatroban significantly inhibited the following OVA-induced allergic features when compared to the nontreated sensitized group: sneezing, nasal rubbing, eosinophil infiltration, IL-16 expressions in nasal tissue, and serum IL-16 level. Serum OVA-specific IgE and local T cell infiltration were reduced, but they did not reach significant values., Conclusions: These results suggest that IL-16 was both systemically and locally upregulated in the murine allergic rhinitis model and that IL-16 changed in parallel to allergic state by treatment with the drugs., (Copyright (C) 2009 S. Karger AG, Basel.)

Allergic rhinitis (AR) affects approximately 500 million people worldwide, and prevalence is increasing. Second-generation nonsedating antihistamines are first-line treatments for seasonal AR (SAR). This study was performed to evaluate early SAR symptom relief with second-generation antihistamines through a retrospective analysis of previously published data. In this study, 835 subjects aged 12-60 years with a > or = 2-year history of SAR were randomized to receive loratadine, 10 mg, once daily; fexofenadine, 60 mg, twice daily; or placebo for 7 days. Each subject recorded the severity of five symptoms of SAR on a scale of 0-3. This primary post hoc efficacy analysis was the mean change from baseline in daily average A.M./P.M. reflective and instantaneous total symptom score (TSS) on days 2 and 3. Significantly greater mean reductions from baseline were shown with loratadine compared with fexofenadine in average A.M./P.M. reflective TSS on days 2 (-3.51 versus -2.84, respectively; p < 0.002) and 3 (-3.80 versus -3.19, respectively; p = 0.007) and in average A.M./P.M. instantaneous TSS on day 3 (-3.68 versus -3.15, respectively; p = 0.022). Similar results were noted in average A.M./P.M. reflective and instantaneous total nasal symptom scores and for 10 of 20 individual symptom time points (p < 0.05). Loratadine was significantly more effective than placebo for all time points (p < 0.001). Early, sustained symptom relief was seen with loratadine, suggesting that it may be more effective for treating SAR symptoms.

Background: Diphenhydramine is often the treatment of choice for acute urticarial or allergic reactions despite its adverse effects of sedation and impairment. Second- and third-generation histamine1-antihistamines are generally devoid of these adverse effects but are typically not used because of a perceived slower onset of action., Objective: To examine the time-dependent effects of oral fexofenadine and oral and intramuscular diphenhydramine to reduce histamine-induced wheal-and-flare responses., Methods: Eighteen healthy patients were included in a double-blind, placebo-controlled, 3-way, randomized, crossover study with oral fexofenadine (180 mg) and oral and intramuscular diphenhydramine (50 mg). Histamine-induced skin tests were performed before and more than 6 hours subsequent to dosing. The primary end point was time to induce a 50% reduction in histamine-induced flare. Secondary end points included change from baseline at each time point in wheal-and-flare responses and area under the curve at more than 6 hours for flare., Results: No significant differences were found in the 50% inhibitory responses of histamine-induced flares among the 3 groups (P = .09). No significant differences were found among the 3 groups in change from baseline at each time point except for 30 minutes during which fexofenadine had no inhibitory effect. Area under the curve analyses for wheal-and-flare responses revealed no differences among treatments at more than 6 hours., Conclusion: Diphenhydramine tended to work more rapidly than fexofenadine, but the differences were not statistically significant. Given the adverse effect profile of diphenhydramine, but only marginal onset of action advantage, the risk-to-benefit ratio may be more favorable for oral fexofenadine when treating an acute urticarial or allergic reaction.

Background: The safety of fexofenadine has been examined extensively in adults and school-age children. However, the safety of fexofenadine in children younger than 6 years has not been reported to date., Objective: To compare the safety and tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in preschool children aged 2 to 5 years with allergic rhinitis., Methods: This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study, conducted between February 29, 2000, and June 14, 2001. Participants were randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily for a 2-week period. To facilitate dosing, capsule content was mixed with applesauce (approximately 10 mL). Safety assessments depended on date of entry into the study because of an amendment to the protocol. Before the amendment, assessments included physical examination, vital signs reporting (oral temperature, heart rate, and respiratory rate), and adverse event (AE) reporting. After the amendment, safety assessments included laboratory testing (blood chemistry and hematology profiles), physical examination, 12-lead electrocardiography, and vital signs (oral temperature, blood pressure, heart rate, and respiratory rate) and AE reporting., Results: Treatment-emergent AEs were observed in 116 of 231 participants receiving placebo and 111 of 222 receiving fexofenadine. These AEs were possibly related to study medication in 19 (8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine, respectively, and most frequently involved the digestive system. No clinically relevant differences in laboratory measures, vital signs, and physical examinations were observed., Conclusions: The findings show that fexofenadine hydrochloride, 30 mg, is well tolerated and has a good safety profile in children aged 2 to 5 years with allergic rhinitis.

Corticosteroids and 5-aminosalicylic acid are the primary standard therapy for inflammatory bowel disease. Recent immunologic data implicate an involvement of mast cell activation followed by increased histamine secretion and elevated tissue concentrations of histamine in the pathogenesis of ulcerative colitis. In the present case, the clinical course of a 35-year-old man with steroid-dependent chronic active ulcerative colitis, who did not respond to high-dose steroids, antibiotics, or azathioprine during 3 years, is reported. Clinical disease activity and established serological markers were recorded during 6 weeks of unsuccessful therapy and during the next 6 weeks, as a new nonsedative antihistaminergic drug, a mast cell stabilizer, and an hypoallergenic diet were implemented in addition to conventional therapy. Induction of remission was achieved within 2 weeks after treatment with fexofenadine, disodium cromoglycate, and an amino acid-based formula. Clinical disease activity, stool frequency, leukocytes, c-reactive protein, and orosomucoid levels in serum decreased rapidly. Daily steroid administration could be gradually reduced along with 6 weeks of this treatment. This report suggests that histamine and mast cell activity may be important pathophysiological factors responsible for persistent clinical and mucosal inflammatory activity in ulcerative colitis despite the use of steroids. In ulcerative colitis, patients unresponsive to conventional treatment, therapeutic considerations should also include an antiallergic approach when further signs of atopy or intestinal hypersensitivity are present.

The present study examined the impact of once-daily fexofenadine hydrochloride (HCl) 180 mg on health-related quality of life (HRQL) in subjects with chronic idiopathic urticaria (CIU). This was a multicenter, randomized, double-blind. parallel-group, placebo-controlled study. Subjects completed the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment (WPAI) questionnaire at baseline and at weeks 2 and 4. The primary HRQL end point was mean change from baseline to week 4 in total DLQI score. Subjects in the fexofenadine HCl treatment group (n = 163) experienced significantly greater improvements in mean total DLQI score (P = .0219) and in the individual domains of symptoms and feelings (P = .0119) and personal relationships (P = .0091) compared with those in the placebo group (n = 91). Subjects who received fexofenadine HCl experienced less work productivity impairment, overall work impairment, and activity impairment than those who received placebo. The results indicated that once-daily fexofenadine HCl 180 mg improved the HRQL of subjects with CIU, as assessed by change in total DLQI score.

To date, no published articles exist comparing the H1-receptor antagonist activities of fexofenadine and desloratadine using the histamine-induced skin wheal-and-flare model. The aim of this study was to compare the efficacy of fexofenadine versus desloratadine in suppressing histamine-induced skin flares and wheals in adults and adolescents. This was a two-center, randomized, placebo-controlled, complete-crossover study. Subjects were administered either single-dose fexofenadine HCl, 180 mg; desloratadine, 5 mg; or placebo and their response to skin-prick testing with histamine and diluent was recorded at predetermined time intervals. The primary end point was change in size of histamine-induced summation skin flares. Secondary end points included change in skin wheal summation measurements, onset, duration, maximum percent suppression, and time to maximum suppression of flares and wheals. Fexofenadine suppressed skin flares significantly more than desloratadine from 2 to 6 hours, and wheals from 2 to 4 hours, 6 to 9 hours, and 12 hours posttreatment. In addition, fexofenadine suppressed flares more than placebo at all time points from 2 to 24 hours and wheals more than placebo at all time points from 2 to 12 hours posttreatment. Desloratadine suppressed flares significantly more than placebo from 6 to 10 hours and at 12 and 24 hours but suppressed wheals significantly versus placebo only at 10 hours. Fexofenadine had a faster onset of flare suppression than desloratadine (1 hour versus 5 hours) and an equally rapid onset of wheal suppression. Fexofenadine HCl, 180 mg, was superior to desloratadine, 5 mg, in histamine-induced wheal-and-flare suppression, suggesting increased in vivo H1-receptor antagonist potency of fexofenadine versus desloratadine.

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.

Background: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR)., Objective: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR., Methods: Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol., Results: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively)., Conclusion: In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

This is the first U.S.-based study to compare efficacy and safety of desloratadine with fexofenadine in subjects with symptomatic seasonal allergic rhinitis (SAR). In this double-blind study, subjects were randomized to desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n = 144) once daily for 15 days. Primary end point was mean change from baseline to study end in morning instantaneous total symptom score (AM NOW TSS) excluding congestion. Secondary measures included change from baseline in the morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR ISS including congestion. Subjects self-evaluated their symptoms on a five-point scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo. Desloratadine and fexofenadine were not statistically different (p = 0.491); the upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS excluding congestion was comparable between desloratadine and fexofenadine (p = 0.405; CI = 0.221) but was significantly greater with both active treatments versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS (both including congestion) versus placebo; reductions were comparable between active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and fexofenadine, 180 mg, provide comparable efficacy and tolerability in the treatment of SAR. Both treatments are significantly more effective than placebo.

Background: Allergen-specific immunotherapy, although not a cure, remains the only treatment available that can alter the natural course of an allergic disease. However, the risk of allergen specific immunotherapy-related systemic reactions (SRs), reported to occur in approximately 1% to 14% of patients and which can range from mild to fatal in seriousness, represents a barrier to implementing this unique and effective treatment option., Objective: To explore the possibility that pretreatment with the H1-antihistamine fexofenadine could prevent the occurrence of severe SRs induced by immunotherapy in Japanese patients with allergic rhinitis., Methods: In this open-label, multicenter study, 134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours before immunization injection (n = 67) or to a control group receiving no pretreatment (n = 67). Patients were further grouped into those who received cedar pollen immunotherapy and those who received dust mite immunotherapy., Results: Pretreatment with fexofenadine 2 hours before immunotherapy significantly reduced the occurrence of severe SRs (P = .03), significantly increased the proportion of patients receiving cedar pollen immunotherapy who achieved the target maintenance dose (TMD) (P = .03), and significantly reduced the length of time to attain the TMD (P = .047 and P = .003 for patients receiving cedar pollen and dust mite immunotherapy, respectively)., Conclusions: This study suggests a novel role for fexofenadine in enhancing the safety of immunotherapy and increasing the proportion of patients achieving the TMD.

Background: To date, it is unknown whether fexofenadine mitigates the worsening of symptoms induced by the cat allergen Felis domesticus allergen 1., Objective: To determine the effects of a single dose of fexofenadine hydrochloride, 180 mg, in preventing and controlling cat allergen-induced allergic rhinitis symptoms using the cat room challenge model., Methods: This single-center, randomized, double-blind, placebo-controlled, 2-way crossover study consisted of a screening visit, 1 or 2 qualifying visits, and 2 treatment periods separated by a mean +/- SD washout period of 14 +/- 3 days. Patients were randomized to treatment sequence 1 (placebo followed by fexofenadine) or sequence 2 (fexofenadine followed by placebo). Baseline end points were obtained before study drug administration, and allergen challenges were initiated 1 1/2 hours after dosing. The primary end point was the change from predose baseline in the total symptom score (sum of rhinorrhea, itchy nose/palate/ throat, sneezing, and itchy/watery/red eyes) after 30 minutes of allergen exposure compared with placebo., Results: Of 211 patients screened, 66 were randomized and 63 completed the study. Mean change in the total symptom score from predose baseline was significantly less with fexofenadine compared with placebo 30 minutes after initiation of the cat allergen challenge (2 hours after dosing) (P = .03). The overall incidence of treatment-emergent adverse events was low and comparable for both groups., Conclusion: Prophylactic treatment with a single dose of fexofenadine hydrochloride, 180 mg, significantly mitigated the worsening of allergic rhinitis symptoms induced by exposure to cat allergen compared with placebo use.

Antihistamines have been used for the treatment of not only allergic diseases such as allergic urticaria and rhinitis, but also of eczematous skin diseases because of their anti-pruritic effects. Moreover, the pruritus associated with eczematous diseases is considered to be induced, in part, by histamine. However, it is unclear whether antihistamines inhibit the itch of eczematous diseases in the absence of topical corticosteroids. In this study, we investigated the anti-pruritic effect of the antihistamine, fexofenadine, on the itch of contact dermatitis that was induced by topical application of diphenylcyclopropenone for the treatment for alopecia areata. Thirteen patients with alopecia areata, who had been treated weekly with topical immunotherapy with diphenylcyclopropenone for 3 months to 2 years, recorded the severity of their itching on a visual analog scale before and 3, 6, 12, 24, 48 and 72 h after application of diphenylcyclopropenone for 4 consecutive weeks. Seven patients took fexofenadine during the first and third weeks, and six patients took fexofenadine during the second and fourth weeks. The severity of itching reached a maximum 6-12 h after the induction of the contact dermatitis in most of the patients. However, fexofenadine partially but rapidly reduced the severity of itching for 72 h during the entire period of treatment in the absence of topical corticosteroids. Our results suggest that fexofenadine can be beneficial in the daily management of patients with itching due to eczematous disease.

Background: Allergic rhinitis is manifested by watery discharge; however its clinical effect on the watery volume in the oral cavity is unknown. In addition, the low incidence of dry mouth due to treatment with the new generation antihistamines is based on subjective patients' reports only. This study aimed to examine the effect of loratadine and fexofenadine on the salivary gland function in patients diagnosed with allergic rhinitis compared to untreated allergic patients and healthy individuals., Methods: A comparative observational study assessed parameters related to the patients' perception of dry mouth as well as clinically observed parameters in fexofenadine-treated patients (group A) and in loratadine-treated patients (group B). Allergic patients without pharmacological treatment (group C) and healthy individuals (group D) served as a double control in order to evaluate the effect of allergy itself on dry mouth. A total of 36 patients were enrolled., Results: Patients in groups A and C reported the highest intensity of xerostomia. Sialometry values were significantly lower in these 2 groups compared to the healthy controls (p = 0.02 and 0.03, respectively). Average sialometry was over 0.2 ml/min in all groups and subjective dry mouth sensation ranged in the lower quarter of the visual analogue scale., Conclusions: In this pilot study, patients diagnosed with allergy presented a significant difference in salivary flow rate compared to healthy controls. Unlike the effect of loratadine, fexofenadine-treated patients showed significantly lower salivary flow rates compared to healthy individuals. In all cases the intensity of dry mouth was low.