olopatadine-hydrochloride and Rhinitis--Allergic--Seasonal

To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR).. The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride.. Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed.. In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID. OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older.. OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

Topics: Administration, Intranasal; Double-Blind Method; Humans; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal; Treatment Outcome

Allergic rhinitis (AR) is a common disease with an important impact on the quality of life and very high management costs. In many patients, the poor control of rhinitis symptoms often requires the use of different drugs, and polytherapy tends to reduce therapeutic adherence. According to the latest version of ARIA guidelines, the currently recommended drugs for the treatment of moderate-to-severe AR are second-generation antihistamines, intranasal corticosteroids, and their combination, even in a single nasal spray device. A single medication with a rapid onset of action, acting on breakthrough symptoms too, would be advantageous, also in terms of patient compliance.. GSP301 (olopatadine 600 µg - mometasone furoate 25 µg) is a novel intranasal formulation, combining the second-generation antihistamine olopatadine hydrochloride with mometasone furoate. Here, we review the evidence for GSP301, especially concerning the efficacy and safety profile of this intranasal combination in the treatment of AR.. The evidence provided in the current review clearly supports the use of GSP301 as a novel intranasal corticosteroid/antihistamine combination with a well-documented efficacy and safety profile in terms of rapid symptom relief and good tolerability.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Anti-Allergic Agents; Drug Combinations; Histamine Antagonists; Humans; Mometasone Furoate; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Treatment Outcome

GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy and safety of GSP301 in the treatment of allergic rhinitis.. A systematic review and meta-analysis were conducted. The data were collected from PubMed, Cochrane Central Register of Controlled Trials and Embase databases till June 2021. In patients with AR, short-term (2/6 weeks) and long-term (52 weeks) effects of GSP301 were assessed. Average morning and evening 12-h reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score(iTOSS), Physician-assessed nasal symptom score (PNSS), rhinoconjunctivitis quality of life (RQLQ), rhinitis control assessment test (RCAT) and adverse events (AEs) were measured.. Five randomized controlled trials were included. GSP301 showed greatly improvement in rTNSS (MD = - 0.99; [95% CI - 1.19 to - 0.79]; P < 0.01; I. GSP301 is a safe and well-tolerated medication. It showed short-term benefits for seasonal and perennial AR, but may not help to improve patients' quality of life and rhinitis control in the long run.

Topics: Administration, Intranasal; Anti-Allergic Agents; Double-Blind Method; Humans; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Treatment Outcome

Allergic rhinitis is an IgE-mediated condition that produces inflammation of the mucosa of the nose, paranasal sinuses and, frequently, of the ocular conjunctiva. Allergic rhinitis causes a significant disease burden in terms of quality of life, lost productivity and medical treatment costs. One of the newest treatments approved by the FDA is Patanase (olopatadine hydrochloride) Nasal Spray, 665 microg/spray (OLO). Olopatadine is an antihistamine with selective H(1)-receptor antagonist activity.. This review details the basic and clinical research on the olopatadine molecule and OLO nasal spray from 1996 to the present day.. The reader will gain a better understanding of the pharmacology of OLO nasal spray, the clinical trial data that have established the efficacy of OLO nasal spray and the overall role of OLO nasal spray in the management of allergic rhinitis.. Olopatadine nasal spray is one of the newest treatments approved by the FDA for the management of allergic rhinitis. OLO has a rapid onset of action, efficacy comparable to intranasal steroid sprays and is approved for seasonal allergic rhinitis in patients aged > or = 6 years.

Topics: Child; Clinical Trials as Topic; Dibenzoxepins; Drug Approval; Histamine H1 Antagonists, Non-Sedating; Humans; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal; Treatment Outcome; United States; United States Food and Drug Administration

To review the literature supporting current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis.. Published articles in the peer-reviewed medical literature.. Clinical trials focusing on the efficacy, safety, and recommended uses of the currently approved nasal antihistamines in the United States: azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%.. Azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%, have rapid onsets of action, are well tolerated, and have clinical efficacy for treating allergic rhinitis that is equal or superior to oral second-generation antihistamines. Both also have a clinically significant effect on nasal congestion. Azelastine is also approved for nonallergic rhinitis. Although older data suggest that intranasal steroids have greater clinical efficacy than nasal antihistamines, more recent comparisons in patients with mild to moderate disease have shown equal or noninferior efficacy. In addition, in contrast to oral antihistamines or leukotriene antagonists, the combination of a nasal antihistamine and intranasal steroid may provide additive benefits for treating patients with more severe disease.. The data support current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis. Future studies should address possible as needed use, the use of premixed antihistamine-steroid combinations, and the treatment of mixed rhinitis.

Topics: Administration, Intranasal; Anti-Allergic Agents; Clinical Trials as Topic; Dibenzoxepins; Humans; Olopatadine Hydrochloride; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.

Topics: Animals; Anti-Allergic Agents; Conjunctivitis, Allergic; Dibenzoxepins; Histamine Antagonists; Humans; Hypersensitivity; Olopatadine Hydrochloride; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate.. To evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR).. This double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 μg and mometasone furoate 25 μg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events.. GSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (-0.6; 95% confidence interval, -0.9 to -0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective "tearing/watering eyes" (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved.. GSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile.. ClinicalTrials.gov Identifier: NCT03463031.

Topics: Administration, Intranasal; Anti-Allergic Agents; Child; Double-Blind Method; Humans; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome

GSP301 is an investigational fixed-dose combination nasal spray of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).. To evaluate efficacy and safety of GSP301 in patients with seasonal AR (SAR).. In this phase 2, double-blind, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to twice-daily GSP301 (olopatadine 665 μg and mometasone 25 μg), once-daily GSP301 (olopatadine 665 μg and mometasone 50 μg), twice-daily or once-daily olopatadine monotherapy (665 μg), mometasone monotherapy (twice-daily 25 μg or once-daily 50 μg), or placebo for 14 days. The primary endpoint-mean change from baseline in morning and evening reflective Total Nasal Symptom Score (rTNSS)-was analyzed using analysis of covariance (ANCOVA; P < .05 = statistically significant). Average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs) were also assessed.. A total of 1111 patients were randomized. Twice-daily GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (P < .001), twice-daily olopatadine (P = .049), and mometasone (P = .004). Similar significant improvements in iTNSS were observed with twice-daily GSP301 vs placebo (P < .001) and twice-daily mometasone (P = .007); improvements were not significant vs olopatadine (P = .058). Once-daily GSP301 provided significant rTNSS and iTNSS improvements vs placebo and once-daily olopatadine (P < .01, all) but improvements were not significant vs mometasone. Treatment-emergent AEs rates were 10.8%, 9.5%, and 8.2%, with twice-daily GSP301, once-daily GSP301, and placebo, respectively.. Twice-daily GSP301 treatment was efficacious and well tolerated, providing statistically significant and clinically meaningful improvements in rTNSS (primary endpoint) vs placebo and both monotherapies.. Clinicaltrials.gov Identifier NCT02318303.

Topics: Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal; Treatment Outcome

GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate intended for seasonal allergic rhinitis (SAR) treatment.. To evaluate the efficacy and safety of once-daily or twice-daily GSP301 in a ragweed pollen environmental exposure chamber.. In this randomized, double-blind, double-dummy study, adults (18-65 years old) with SAR were equally randomized to 665 μg of olopatadine and 25 μg of mometasone (twice-daily GSP301), 665 μg of olopatadine and 50 μg of mometasone (once-daily GSP301), a US Food and Drug Administration-approved formulation of 137 μg of azelastine and 50 μg of fluticasone twice-daily (AzeFlu), a US Food and Drug Administration-approved formulation of 665 μg of olopatadine twice-daily, or placebo (twice-daily). During 2 visits (baseline and end of 14-day treatment), participants assessed SAR symptoms at specified time points. The primary end point-mean change from baseline in instantaneous total nasal symptom score (iTNSS) for twice-daily or once-daily GSP301 vs placebo-was analyzed by analysis of covariance. Onset of action, ocular symptoms, and adverse events were assessed.. A total of 180 participants were randomized. Treatment with twice-daily or once-daily GSP301 provided statistically significant improvements in iTNSS vs placebo (twice-daily GSP301: least squares mean difference, -3.60; 95% confidence interval [CI], -4.89 to -2.30; once-daily GSP301: least squares mean difference, -3.05; 95% CI, -4.35 to -1.76; P < .0001 for both). Significant improvements in iTNSS with twice-daily GSP301 occurred by 10 minutes after dosing (-1.26; 95% CI, -2.30 to -0.21; P = .02) and were maintained at all later time points except one (2.5 hours). Treatment-emergent adverse events occurred in 22.2%, 30.6%, 25.0%, 22.2%, and 16.7% of participants in the twice-daily GSP301, once-daily GSP301, AzeFlu, olopatadine, and placebo groups, respectively.. In an environmental exposure chamber model, twice-daily and once-daily GSP301 treatments were well tolerated and provided statistically significant and clinically meaningful SAR symptom improvement vs placebo.. ClinicalTrials.gov Identifier: NCT03444506.

Topics: Adult; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Environmental Exposure; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal

GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).. To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR).. In this double-blind study, eligible patients (≥12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 μg of olopatadine and 25 μg of mometasone), olopatadine (665 μg), mometasone (25 μg), or placebo for 14 days. The primary end point-mean change from baseline in average morning and evening 12-hour reflective Total Nasal Symptom Score (rTNSS)-was analyzed via a mixed-effect model repeated measures (P < .05 was considered to be statistically significant). Additional assessments included average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs).. A total of 1176 patients were randomized. GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (least squares mean difference, -1.09; 95% CI, -1.49 to -0.69; P < .001) and vs olopatadine (P = .03) and mometasone (P = .02). Similar significant improvements in iTNSS were also observed with GSP301 (P < .05 for all). Furthermore, GSP301 significantly improved overall ocular symptoms, individual nasal and ocular symptoms, and quality of life vs placebo (P ≤ .001 for all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent timepoints. Treatment-emergent AEs occurred in 15.6%, 12.6%, 9.6%, and 9.5% of patients in the GSP301, olopatadine, mometasone, and placebo groups, respectively.. GSP301 is efficacious and well tolerated vs placebo for treating SAR-associated nasal and ocular symptoms, with a rapid onset of action of 15 minutes in adult and adolescent patients 12 years and older.. ClinicalTrials.gov: NCT02870205.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Disease Progression; Double-Blind Method; Drug Combinations; Female; Histamine Antagonists; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome; Young Adult

Topics: Adult; Anti-Allergic Agents; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Placebos; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome

GSP301 is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray.. To assess the relative bioavailability of olopatadine administered as GSP301 versus two olopatadine monotherapy nasal spray formulations.. In this single-dose, open-label, crossover study, healthy adults (18-65 years old) were equally randomized to one of six treatment sequences for three 48-hour treatment periods with GSP301 (olopatadine 665 μg-mometasone 50 μg), the olopatadine monotherapy component of GSP301 (OLO-sponsor; 665 μg) and U.S. Food and Drug Administration approved olopatadine (OLO; 665 μg); each treatment was administered as a single dose (two sprays in each nostril). To assess the relative bioavailability of olopatadine in the fixed-dose nasal spray versus two monotherapies, pharmacokinetic (PK) estimates, maximum plasma concentration (Cmax), area under the plasma concentration time curve (AUC) from time 0 to the last time point with measurable concentration (AUC0-t), and AUC from time 0 to time infinity (AUC0-∞) were compared by analysis of variance. Safety and tolerability were also evaluated.. A total of 30 healthy adults (mean age, 43.1 years) were randomized. The majority of the subjects were white men. The geometric mean ratios for natural log transformed Cmax, AUC0-t, and AUC0-∞ of olopatadine in GSP301 and OLO-sponsor were 86.63, 86.92, and 92.83, respectively. For GSP301 and OLO, geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 84.68, 87.87, and 93.80, respectively. The percentage of subjects who reported treatment-emergent adverse events (AE) for GSP301, OLO-sponsor, and OLO were 13.8, 10.3, and 10.0%, respectively, with mild AEs reported. One subject withdrew from the study due to an AE (minor oropharyngeal pain) during OLO treatment, before receiving GSP301.. Olopatadine bioavailability with GSP301 was comparable with OLO-sponsor and OLO. The presence of mometasone in GSP301 did not considerably affect the PK of olopatadine. GSP301 was well tolerated, with only mild AEs reported.

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Cross-Over Studies; Drug Combinations; Female; Healthy Volunteers; Histamine Antagonists; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal; Young Adult

Epinastine hydrochloride is a selective histamine H1 receptor antagonist that also inhibits IgE receptor-mediated histamine release from mast cells.. To show the superiority of epinastine 0.05% ophthalmic solution (epinastine) to placebo ophthalmic solution (placebo) and noninferiority to olopatadine 0.1% ophthalmic solution (olopatadine) for cedar pollen antigen-induced ocular itching and conjunctival hyperemia.. The study was conducted in ophthalmologically asymptomatic adult volunteers with seasonal allergic conjunctivitis using a conjunctival allergen challenge test. Subjects were randomized into 3 groups (n = 87) to evaluate superiority to placebo (visits 4 to 6) and 2 groups (n = 86) to evaluate noninferiority to olopatadine (visit 7). At each visit, a single administration of the study medication was instilled at 15 minutes (visit 4), 4 hours (visit 5), 8 hours (visit 6), and 4 hours (visit 7) before the conjunctival allergen challenge test. Ocular itching and conjunctival hyperemia of allergic conjunctivitis were assessed after the conjunctival allergen challenge test.. For the primary end point, epinastine showed superiority to placebo for the inhibition of ocular itching and conjunctival hyperemia induced at 4 hours after the dose (equivalent to 4-times-daily dosing). For the secondary end points, epinastine significantly inhibited itching and conjunctival hyperemia induced at 15 minutes and 8 hours after the dose (equivalent to 2-times-daily dosing) compared with placebo. In addition, epinastine demonstrated noninferiority to olopatadine for ocular itching and conjunctival hyperemia. No adverse drug reactions or serious adverse events were reported throughout the study, indicating that epinastine has a good safety profile.. Epinastine is effective and safe for the treatment of allergic conjunctivitis.. Clinicaltrials.gov identifier NCT01363700.

Topics: Adult; Allergens; Anti-Allergic Agents; Cedrus; Conjunctiva; Conjunctivitis, Allergic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Humans; Hyperemia; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Platelet Aggregation Inhibitors; Pollen; Rhinitis, Allergic, Seasonal; Young Adult

Nasal allergen challenge (NAC) leads to a nasal ocular reflex, which is augmented by allergic inflammation. This study was designed to confirm our previous observation that an intranasal steroid inhibits the nasal ocular reflex and to show that histamine does not play an important role in the genesis of this reflex.. We performed a randomized, double-blind, double-dummy, placebo (PL)-controlled, four-way crossover trial in subjects with seasonal allergic rhinitis out of season. Subjects were randomized to receive 1 week pretreatment with intranasal PL and intraocular (PL/PL), intranasal PL and intraocular olopatadine (PL/OLO), intranasal fluticasone furoate (FF) and intraocular PL (FF/PL), and the combination (FF/OLO). Subjects then underwent NAC on 2 consecutive days. The number of sneezes and nasal and ocular symptoms were recorded, and levels of tryptase and histamine were measured in nasal lavages.. NAC after PL/PL resulted in increase in symptoms, histamine, and tryptase after the challenge on the 2nd day. There was a reduction in eye symptoms on the 2nd day of challenge from 6.0 after PL/PL to 0 after FF/PL (p = 0.001), 2.5 after PL/OLO (p = 0.3), and 1.5 after FF/OLO (p = 0.003). Furthermore, there was no significant difference between the response after FF/PL versus FF/OLO and a significant difference between FF/PL and PL/OLO (p = 0.02). Levels of tryptase followed a similar trend. The number of eosinophils in nasal lavages on the 2nd day of challenge were also reduced by the treatment arms containing FF compared with PL.. Our data confirm the existence of a nasal ocular reflex after NAC. OLO alone or the addition of OLO to FF does not impact ocular symptoms caused by the naso-ocular reflex, suggesting that mast cells are not activated to release histamine in the conjunctiva during this process.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Cross-Over Studies; Dibenzoxepins; Disease Progression; Drug Therapy, Combination; Eosinophils; Eye; Female; Histamine; Humans; Injections, Intraocular; Male; Middle Aged; Nose; Olopatadine Hydrochloride; Reflex; Rhinitis, Allergic, Seasonal; Young Adult

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.

Topics: Adolescent; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Olopatadine Hydrochloride; Promethazine; Pruritus; Psychomotor Performance; Rhinitis, Allergic, Seasonal; Terfenadine; Urticaria; Young Adult

The efficacy of antihistamines in perennial allergic rhinitis in children has been evaluated in studies using active comparators, whereas placebo-controlled studies are very few. A randomized, multicenter, double-blind, parallel-group clinical study was carried out to evaluate the dose-response relationship and superiority of olopatadine hydrochloride over placebo in children aged 7 to 16 years with perennial allergic rhinitis.. Subjects received twice daily treatment for two weeks with either olopatadine 2.5 mg, 5 mg or placebo after a one-week observation period. Efficacy was assessed based on the diary card score the subject (or guardian) recorded.. Of the 302 subjects randomized, two were excluded from analysis: one did not receive treatment; the other was not monitored for efficacy parameters. The remaining 300 subjects (97 in the placebo group, 103 in the olopatadine 2.5-mg group and 100 in the olopatadine 5-mg group) constituted the full analysis set (FAS) for the efficacy analysis. As a primary endpoint, the total three nasal symptom score (for sneezing, rhinorrhea and nasal congestion) at final assessment was compared with baseline or the score obtained in the observation period. The change from baseline was then tested using analysis of covariance (ANCOVA) with the baseline score as covariate. Williams' test was applied to the least squares means estimated from this ANCOVA model for each treatment group, resulting in showing the monotonicity Williams' test assumed. The total three nasal symptom score significantly improved in the 5-mg group compared with the placebo group (p = 0.019). In contrast, the 2.5-mg group did not differ statistically from the placebo group. Adverse events occurred in 33.7% (33/98 subjects) in the placebo group, 35.9% (37/103 subjects) in the 2.5-mg group and 35.0% (35/100 subjects) in the 5-mg group. There were no serious or severe adverse events.. Olopatadine hydrochloride 5 mg twice daily is an effective and safe treatment for perennial allergic rhinitis in children.

Topics: Adolescent; Algorithms; Anti-Allergic Agents; Child; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Olopatadine Hydrochloride; Patient Participation; Placebos; Rhinitis, Allergic, Seasonal; Treatment Outcome

Seasonal allergic rhinitis (SAR) is an allergen-induced inflammatory reaction that occurs during periods of high pollen count. Current treatments for SAR include allergen avoidance, systemic antihistamines, and steroidal and nonsteroidal intranasal sprays. Olopatadine is a selective antihistamine and an inhibitor of proinflammatory mediators from human mast cells. An intranasal formulation of olopatadine has been developed for the treatment of SAR.. The aim of this study was to compare the efficacy and tolerability of olopatadine hydrochloride nasal spray 0.6% (OLO) relative to azelastine hydrochloride nasal spray 0.1% (AZE) and an inactive vehicle in the treatment of SAR.. This Phase III, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group study was conducted at 21 centers across the United States. Eligible patients were aged > or =12 years and had a history of SAR and verified allergy to a prevalent local allergen. After a run-in period during which inactive vehicle was administered, patients were randomly assigned to OLO, AZE (active control), or inactive vehicle (identical to OLO; placebo control), 2 sprays in each nostril BID for 16 days. The timing of enrollment was correlated with the start of the allergy season at each site. Symptoms were recorded twice daily in an electronic diary. Efficacy assessments included changes in mean daily reflective total nasal symptom scores (TNSS). Tolerability was evaluated based on adverse events (AEs) and nasal, physical, and cardiovascular parameters.. A total of 544 patients were randomized. The mean age was 36 years (range, 12-77 years); men and boys represented 32.2% of the population; and the patients were predominantly white (75.4%). The mean reductions from baseline in reflective TNSS were 26.8%, 29.9%, and 18.4% with OLO, AZE, and inactive vehicle, respectively (P = 0.003 OLO vs inactive vehicle; 95% CI, -2.5% to 8.7% OLO vs AZE [non-inferiority]). The most commonly reported treatment-related AE in the OLO and AZE groups was bitter taste (12.2% [22/180] and 19.7% [37/188], respectively). The prevalence and intensity of bitter taste were significantly lower with OLO than with AZE (P = 0.05 and P = 0.005, respectively). In the group that received inactive vehicle, the prevalence of bitter taste was 1.7% (3/176). The prevalences of other treatment-related AEs, including epistaxis and nasal discomfort, were < or =3.7% in each group and did not differ significantly between groups.. In this small study in patients aged > or =12 years with SAR, the percentage reduction from baseline in TNSS was significantly greater with OLO (2 sprays in each nostril BID) compared with vehicle and not significantly different from that with AZE. OLO and AZE were similarly well tolerated, with the exception of prevalence and intensity of bitter taste, which were significantly lower with OLO.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Allergic Agents; Child; Dibenzoxepins; Double-Blind Method; Epistaxis; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Phthalazines; Rhinitis, Allergic, Seasonal; Taste; United States; Young Adult

Second-generation oral H1-antihistamines have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis; however, the effect of olopatadine has not been widely reported to date.. To evaluate the efficacy of 2 oral H1-antihistamines, olopatadine and fexofenadine, in the treatment of the nasal symptoms of Japanese cedar pollinosis and their possible side effects.. This was a randomized, double-blind, placebo-controlled, crossover study conducted in an environmental exposure unit (EEU). Twenty volunteers suffering from Japanese cedar pollinosis were randomly divided into 3 groups and exposed to cedar pollen in the EEU with oral administration of olopatadine hydrochloride (5 mg), fexofenadine hydrochloride (60 mg), or placebo 1 hour prior to pollen exposure. Nasal symptoms, activity impairment, and subjective sleepiness were self-assessed during the study period. Attention was measured using the digit cancellation test. The trial was repeated after 4 and 7 weeks.. Compared with placebo, olopatadine significantly improved nasal symptoms and activity impairment during pollen exposure (P < .05). There was no significant relief of nasal discharge or nasal congestion with fexofenadine throughout the 5-hour exposure to cedar pollen. Furthermore, olopatadine significantly reduced nasal congestion during the first 2 hours, as well as sneezing and nasal discharge 4 hours after admission to the EEU compared with fexofenadine (P < .05). There was no significant difference in the effect on subjective sleepiness among the 3 groups, and all 3 agents had little effect on attention.. These findings suggest that olopatadine is more effective than placebo and fexofenadine in improving nasal symptoms of Japanese cedar pollinosis.

Topics: Adult; Allergens; Cryptomeria; Dibenzoxepins; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Motor Activity; Olopatadine Hydrochloride; Pollen; Rhinitis, Allergic, Seasonal; Sleep; Sneezing; Terfenadine; Treatment Outcome

Olopatadine, an antihistamine used in allergic conjunctivitis, is under development as a nasal preparation for the treatment of allergic rhinitis.. To evaluate the efficacy of olopatadine in suppressing symptoms and biomarkers of the immediate reaction induced by nasal allergen provocation and to compare olopatadine with azelastine in the same model.. The study was approved by the Johns Hopkins University institutional review board, and all subjects gave written consent. We studied 20 asymptomatic subjects with seasonal allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%. In a third exploratory phase, olopatadine, 0.1%, was compared with topical azelastine, 0.1%, in a patient-masked design. Efficacy variables were the allergen-induced sneezes, other clinical symptoms, and the levels of histamine, tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in nasal lavage fluids.. Both concentrations of olopatadine produced significant inhibition of all nasal symptoms, compared with placebo. Olopatadine, 0.1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine, albumin, and lysozyme. The effects of olopatadine, 0.1%, were comparable to those of azelastine, 0.1%.. Olopatadine, at 0.1% and 0.2% concentrations, was effective in suppressing allergen-induced nasal symptoms. At 0.2%, olopatadine provided evidence suggestive of inhibition of mast cell degranulation.

Topics: Adult; Allergens; Anti-Allergic Agents; Conjunctivitis, Allergic; Cross-Over Studies; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Provocation Tests; Olopatadine Hydrochloride; Phthalazines; Rhinitis, Allergic, Seasonal

Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This study was conducted to evaluate the onset and duration of action of three concentrations of olopatadine nasal spray.. This was a randomized, double-blind, single-dose, placebo-controlled study, conducted in an environmental exposure chamber in patients with SAR. A total of 320 patients were exposed to ragweed allergen in the chamber and randomized to olopatadine nasal spray 0.2%, 0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy, and stuffy nose) were self-assessed during a 12-hour study period.. All concentrations of olopatadine nasal spray provided clinically meaningful reductions in total nasal symptom scores at 30 minutes compared to the placebo. Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than placebo nasal spray at all time-points starting at 90 minutes post-dose and continuing over 12 hours.. Olopatadine nasal spray 0.6% demonstrated a fast onset of action and maintained an effect for at least 12 hours after dosing.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Aged; Allergens; Ambrosia; Anti-Allergic Agents; Dibenzoxepins; Double-Blind Method; Environment, Controlled; Environmental Exposure; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Patient Satisfaction; Placebos; Pollen; Rhinitis, Allergic, Seasonal; Safety; Time Factors; Treatment Outcome

Allergic rhinoconjunctivitis patients are often treated with nasal or systemic allergy therapy, forgoing therapy for ocular symptoms. This treatment regimen leaves important aspects of the allergic reaction untreated and affects quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire and the Allergic Conjunctivitis Quality of Life Questionnaire quantify separate aspects of QoL.. To determine the benefit gained in QoL, measured by these questionnaires, when antiallergy eyedrops (olopatadine) were added to patients' preexisting regimens of nasal or systemic allergic rhinitis treatment.. This was a 4-week prospective, multicenter, open-label, crossover, environmental QoL study. Visit 1 randomized patients to treatment group A or B and included baseline examinations and questionnaires. Group A instilled olopatadine twice daily and concomitantly with previously prescribed nasal or systemic antiallergy medication for 2 weeks. Group B received no ocular therapy and used only previously prescribed antiallergy medication for 2 weeks. Treatment group crossover occurred at visit 2. Patients again completed the questionnaires at visits 2 and 3.. Two hundred patients completed the study, 97 in group A and 103 in group B. Groups A and B experienced ocular allergic symptoms for 3.88 and 3.96 days, respectively, during the week before baseline. At visits 2 and 3, questionnaire scores were significantly improved for each group when olopatadine was added compared with the nontreatment periods. By visit 2, olopatadine improved QoL by 49% compared with 5% in the nontreated group (P < .001).. In this study, 90.5% of patients with allergic rhinitis treated nasally or systemically also had ocular allergic symptoms. Adding olopatadine to these patients' medication regimens significantly improved ocular allergic symptoms and overall QoL.

Topics: Administration, Intranasal; Adult; Anti-Allergic Agents; Cross-Over Studies; Dibenzoxepins; Drug Administration Schedule; Humans; Male; Multicenter Studies as Topic; Olopatadine Hydrochloride; Ophthalmic Solutions; Prospective Studies; Quality of Life; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Treatment Outcome; United States

A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar.. To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar.. This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms.. Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo.. Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Child; Demography; Dibenzoxepins; Female; Humans; Juniperus; Male; Middle Aged; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal; Treatment Outcome

The most common form of allergic ocular disease is seasonal allergic conjunctivitis, coinciding with the pollen season and generally associated with rhinitis. Symptoms of allergic conjunctivitis include ocular itching, hyperemia, tearing, mucus production, foreign body sensation, chemosis, and lid edema. Similarly, the primary symptoms of allergic rhinoconjunctivitis are nasal itching, irritation, sneezing, watery rhinorrhea, and congestion combined with ocular itching, tearing, and swelling.. This study compared olopatadine 0.1% ophthalmic solution with placebo eyedrops (over-the-counter artificial tear product), instilled in the eye, with regard to the prevention and relief of the ocular and nasal symptoms of seasonal allergic conjunctivitis and rhinoconjunctivitis.. This was a randomized, double-blind, parallel-group study, conducted at 7 US centers, to instill either olopatadine 0.1% ophthalmic solution or placebo eyedrops (artificial tears) in both eyes twice daily for 10 weeks. Patients were evaluated for efficacy (intent-to-treat) and safety. Only patients with proven grass pollen allergy (dermal and conjunctival allergen challenge tests) were selected; all patients were studied during the same period, historically shown to be grass season; and grass pollen counts were obtained.. A total of 131 patients (64 olopatadine; 67 placebo) were assessed for efficacy (intent-to-treat); 132 patients were assessed for safety. The mean (SD) age of participants was 38.53 (11.61) years (range, 18 to 87 years), and 58.0% were women (76/131), with no significant differences between groups for age or sex. In the olopatadine group, 1.6% of patients were black (1/64), compared with 14.9% of the placebo group (10/67) (P = 0.005). Mean scores of ocular itching and hyperemia were lower at all assessment times with olopatadine than placebo. The difference was statistically significant (P < 0.05) for itching on days 7, 14, 35, 63, and 70, and for hyperemia on days 14, 28, 42, and 63, after correction for multiplicity. Linear regression slopes predicting ocular itching and hyperemia from the pollen count were significantly lower (P < 0.003 and P < 0.035, respectively) with olopatadine than with placebo. Similar results were obtained for rhinorrhea, sneezing, and nasal itching (P < 0.006, P < 0.012, and P < 0.034, respectively). With placebo, the proportion of patients with frequent ocular itching and hyperemia increased as a function of pollen level; however, with olopatadine, the proportions remained low and virtually constant.. In the population studied, olopatadine 0.1% ophthalmic solution controlled ocular and nasal symptoms of allergic conjunctivitis and rhinocojunctivitis and was well tolerated when administered twice daily for 10 weeks.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Rhinitis, Allergic, Seasonal; Seasons

The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10 mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12 min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P = 0.001 and P = 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P < 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.

Topics: Adult; Airway Resistance; Cross-Over Studies; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Nasal Provocation Tests; Olopatadine Hydrochloride; Placebos; Rhinitis, Allergic, Seasonal; Skin Tests; Sleep Stages; Sneezing; Terfenadine

Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures.. To inform study design for EEU trials evaluating antiallergic therapies.. In this prospective study, 76 participants with birch allergy experienced 3 exposures to birch pollen: (1) an out-of-season EEU challenge (two 3-hour sessions on consecutive days); (2) a natural seasonal exposure; and (3) an in-season EEU challenge (3-hour exposure for 2 weeks after birch pollen season initiation).. The total nasal symptom score, total ocular symptom score, and total symptom score (TSS = total nasal symptom score plus total ocular symptom score) were assessed every 30 minutes and daily during EEU and natural exposures. A high association between TSSs and day 2 of the out-of-season and in-season EEU challenges was noted, with a good association between the maximum TSS during the natural and in-season EEU challenges, and natural season and day 2 of the out-of-season EEU challenge (P < .001 for all). Participants had higher maximum change from the baseline TSS during day 2 of the out-of-season EEU challenge (12.4) vs the following: (1) first day (9.8); (2) in-season EEU challenge (8.4); and (3) natural seasonal exposure (7.6) (P < .001 for all).. A strong association was seen between the presence of allergy symptoms and exposure to birch pollen in the EEU (maximum change in symptom scores during day 2) and in the field. A hybrid trial design may be useful to demonstrate the clinical efficacy of novel antiallergic therapies requiring fewer participants and shorter timelines and expediting treatment availability.

Topics: Adult; Allergens; Anti-Allergic Agents; Betula; Cetirizine; Environmental Exposure; Female; Humans; Male; Mometasone Furoate; Olopatadine Hydrochloride; Pollen; Prospective Studies; Rhinitis, Allergic, Seasonal; Seasons; Severity of Illness Index

Olopatadine hydrochloride nasal spray (Patanase Nasal Spray, Alcon Laboratories, TX, USA) was approved by the US FDA in 2008, and is indicated for the relief of symptoms of seasonal allergic rhinitis (SAR), also referred to as allergic rhinosinusitis. Olopatadine is an antihistamine with selective H1-receptor antagonist activity. Clinical trials of olopatadine nasal spray have demonstrated safety and efficacy in the treatment of SAR patients. With an onset of action of 30 min, olopatadine nasal spray has also been shown to improve quality of life, ability to perform work and the conduct of usual activities in SAR patients.

Topics: Activities of Daily Living; Administration, Intranasal; Clinical Trials as Topic; Dibenzoxepins; Drug Approval; Epistaxis; Histamine H1 Antagonists, Non-Sedating; Nasal Obstruction; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic, Seasonal

Topics: Administration, Inhalation; Anti-Allergic Agents; Dibenzoxepins; Humans; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal

It is well known that starting treatment for cedar pollinosis therapy with second-generation antihistamines before the initial day of pollen scattering can relieve nasal symptom severity during the pollen season. Olopatadine hydrochloride (olopatadine) is an antiallergic agent with histamine H(1) receptor antagonistic action. We have evaluated the effects of repeated preadministration of olopatadine on the toluene-2,4-diisocyanate-induced rhinitis in rats. A single administration of olopatadine suppressed sneezing and the increases in histamine, nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) production in nasal lavage fluid. When olopatadine was administered repeatedly once a day for 7 days before provocation, its inhibitory effects were enhanced compared to the effect of a single administration. Although the repeated administration of fexofenadine enhanced the inhibitory effects on sneezing, it did not inhibit the increases in NGF and VEGF production. These results show that the suppression of the increase in NGF and VEGF might partially be involved in the improvement of nasal allergy signs by the treatment with olopatadine. It is expected that the early treatment with olopatadine may achieve stable therapeutic effects.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Dibenzoxepins; Disease Models, Animal; Drug Administration Schedule; Histamine H1 Antagonists, Non-Sedating; Male; Nerve Growth Factor; Olopatadine Hydrochloride; Rats; Rats, Inbred BN; Rhinitis, Allergic, Seasonal; Terfenadine; Toluene 2,4-Diisocyanate; Vascular Endothelial Growth Factor A

Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Butyrophenones; Cetirizine; Child; Chlorpheniramine; Dermatitis, Atopic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Imidazoles; Japan; Male; Middle Aged; Olopatadine Hydrochloride; Pain Measurement; Piperidines; Population Surveillance; Psychomotor Performance; Pyridines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Surveys and Questionnaires; Terfenadine; Urticaria

CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy.. HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.. The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups.. This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Butyrophenones; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines, CC; Child; Dibenzoxepins; Dose-Response Relationship, Drug; Epithelial Cells; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Mucosa; Olopatadine Hydrochloride; Piperidines; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The effect of KW-4679 (Z)-11-[3-(dimethylamino) propylidene]-6,11-dihydrodibenz [b,e] oxepin-2-acetic acid hydrochloride, CAS 140462-76-6; proposed INN: olopatadine) on experimental conjunctivitis and rhinitis was studied in comparison with that of ketotifen (CAS 34580-14-8) using guinea pigs and rats, respectively. KW-4679 was effective in inhibiting the antigen- and histamine-induced conjunctivitis by both oral and topical administrations. These effects of KW-4679 were somewhat more potent than those of ketotifen. KW-4679 as well as ketotifen was more effective in inhibiting the histamine-induced conjunctivitis than that seen in antigen-induced conjunctivitis when they were given topically. KW-4679 inhibited the increased dye leakage into the nasal cavity induced not only by antigen in actively sensitized rats but also by histamine perfusion in non-sensitized rats by oral and topical administrations. Similar to ketotifen, the effect of KW-4679 on histamine-induced increase in dye leakage was almost same as that induced by antigen. The potency of KW-4679 was higher than that of ketotifen in the increased dye leakage induced by both antigen and histamine perfusion.

Topics: Administration, Oral; Administration, Topical; Allergens; Animals; Anti-Allergic Agents; Ascaris; Conjunctivitis, Allergic; Dibenzoxepins; Guinea Pigs; Histamine; Male; Olopatadine Hydrochloride; Rats; Rats, Wistar; Rhinitis, Allergic, Seasonal