piperidines and Rhinitis--Allergic--Seasonal

Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

Topics: Automobile Driving; Benzimidazoles; Cardiovascular Diseases; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Urticaria

A therapeutic role for histamine H(3) receptor antagonism in allergic rhinitis has been proposed and may be complimentary to the well-known benefits of H(1) receptor antagonism. Combined H(1)/H(3) blockade has therefore been investigated as a novel therapeutic approach that may enhance symptom relief, particularly nasal blockage.. Two novel H(1)/H(3) dual receptor antagonists were investigated in phase I and II safety and efficacy studies. One molecule (GSK1004723) was designed for intranasal administration as a suspension or solution and the other molecule (GSK835726) for oral administration. In phase I and II studies, both molecules were compared with an active control and/or placebo in randomised studies. In phase II studies, efficacy was assessed in an environmental allergen challenge chamber (ECC). Subjects with seasonal allergic rhinitis were exposed to allergen to induce symptoms. Efficacy and safety was measured over 4, 7 and 20-24 h post-dose. The endpoints included total nasal symptom score and nasal blockage.. Intranasal suspension of GSK1004723 and oral GSK835726 were well tolerated. Single-dose intranasal suspensions of GSK1004723 (220, 1,100 μg) failed to demonstrate clinically significant attenuation of symptoms of allergic rhinitis induced in the ECC. Single (10, 50, 100 mg) and 3-day repeat (10 mg) dose oral GSK835726 demonstrated clinically significant attenuation of symptoms in the ECC comparable to cetirizine 10 mg. Three-day repeat dosing of the intranasal solution GSK1004723 1,000 μg also demonstrated a statistically significant attenuation of nasal symptoms, but was less than seen with cetirizine and GSK835726 and caused initial nasal discomfort.. Combined H(1)/H(3) antagonism did not show differentiation from H(1) antagonism in reducing total nasal symptom score or nasal blockage.

Topics: Administration, Intranasal; Anti-Allergic Agents; Cetirizine; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Female; Histamine H1 Antagonists; Histamine H3 Antagonists; Humans; Male; Naphthalenes; Nasal Obstruction; Phthalazines; Piperidines; Rhinitis, Allergic, Seasonal

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Topics: Animals; Automobile Driving; Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria; Wakefulness

This application claims dual receptor specificity antihistamines, active as H(1) and H(3) antagonists, which additionally have a long duration of action that renders them suitable for once daily administration via inhalation for the treatment of allergic rhinitis. The compounds lack CNS penetration and have a high affinity for both histamine receptors.

Topics: Animals; Histamine H1 Antagonists; Histamine H3 Antagonists; Humans; Naphthalenes; Patents as Topic; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship

New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements.. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria.. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

Topics: Animals; Benzimidazoles; Clinical Trials, Phase I as Topic; Histamine H1 Antagonists; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Urticaria

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.

Topics: Benzimidazoles; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Nasal Obstruction; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The evaluation of quality of life (QoL) and its modification through therapeutic interventions has become a prioritary concern in recent years and a requirement on the part of regulatory agencies for the authorization of new drugs. In clinical studies of allergic disorders, particularly allergic rhinitis and urticaria, different types of generic questionnaires have been used - especially disease specific instruments such as the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) or skin disease specific tools such as the Dermatology Life Quality Index (DLQI). Throughout its clinical development, bilastine has been shown to be more effective than placebo and at least as effective as cetirizine, levocetirizine, fexofenadine or desloratadine in controlling the symptoms of seasonal allergic rhinitis and chronic urticaria. QoL has been studied as a secondary objective in three allergic rhinitis clinical trials, using the RQLQ, in a total of 2335 patients. Likewise, in chronic urticaria, QoL has been evaluated using the DLQI in a total of 525 patients, versus levocetirizine and placebo. The improvement in the QoL parameters in these studies (RQLQ or DLQI domains) at all times proved proportional to the symptoms improvement. In general, the data obtained relating to changes in QoL are concordant with the mean global visual analog scale (VAS in mm) values and their changes, from the beginning until the end of the treatment period, for all of the trials, for bilastine and all its comparators.

Topics: Benzimidazoles; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Ocular symptoms often accompany allergic rhinitis and can be as or even more bothersome for the patient than the actual nasal symptoms. Ocular manifestations of allergic rhinoconjunctivitis may result from both direct allergen-mediated mast cell stimulation on the surface of the eye and naso-ocular reflexes--histamine being one of the mediators of symptoms onset. An H1 antihistamine would be the first line treatment for allergic conjunctivitis. Since allergic conjunctivitis is always (or almost always) accompanied by nasal symptoms, a second-generation H1 antihistamine administered via oral route is the drug of choice for jointly managing both the nasal and the ocular symptoms--minimizing the impact of the effects inherent to first-generation H, antihistamine, including particularly drowsiness. Bilastine is a new H1 antihistamine with an excellent safety profile, developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. This new drug has been shown to be effective in controlling the ocular symptoms of allergic rhinoconjunctivitis.

Topics: Benzimidazoles; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Immunoglobulin E; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The following paper reviews the latest news on antihistamines used in the treatment of allergic rhinitis. It describes the new results of investigations on clinical application of H3 and H4 receptors in therapy of allergic diseases as well as the effect of emedastine on histamine-induced tissue remodeling. Contemporary clinical research of these drugs fulfills the requirements of placebo-controlled trials, including the comparison with a reference drug, usually cetirizine. The paper discusses efficacy and safety of a new drug--bilastine, and the possibility to improve clinical outcome by combining antihistamine drugs with inhaled glucocorticosteroids and antileukotrienes. It also presents the studies on high efficacy of nasal antihistamines, which most probably results from their high concentration in inflamed tissue, as well as describes the latest news on safe use of antihistamines, including studies of fexofenadine enantiomers in drug interactions with P-glycoprotein, safety of a new antihistamine medication--rupatadine, and psychostimulating effect of some other antihistamines. The review shows that antihistamines, the most frequently used class of anti-allergy medications, have been constantly improved, which is of significant importance for progress of allergic diseases treatment.

Topics: Administration, Inhalation; Anti-Allergic Agents; Benzimidazoles; Clinical Trials as Topic; Drug Combinations; Glucocorticoids; Histamine Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Histamine is a key mediator in the development of allergy symptoms, and oral H(1)-antihistamines are among the most widely used treatments for symptomatic relief in conditions such as allergic rhinitis and chronic urticaria. Ebastine is a second-generation antihistamine which has been shown to be an effective treatment for both seasonal and perennial allergic rhinitis. In controlled clinical trials in adult and adolescent patients with allergic rhinitis, ebastine 10 mg once-daily improved symptoms to a significantly greater extent than placebo and to a similar extent as loratadine 10 mg and cetirizine 10 mg (both once-daily), while ebastine 20 mg proved to be more effective than these two comparator antihistamines. In addition, ebastine was significantly more effective than placebo at relieving the symptoms of chronic idiopathic urticaria. Ebastine provides efficacy throughout the 24-h dosing interval with once-daily administration and clinical benefit is seen from the first day of treatment. Small studies have found beneficial effects for ebastine in patients with other disorders, including cold urticaria, dermographic urticaria, atopic asthma, mosquito bites and (in combination with pseudoephedrine) the common cold. In addition to the regular ebastine tablet, a fast-dissolving tablet (FDT) formulation, which disintegrates in the mouth without the aid of a drink, is also available. It has been shown to be bioequivalent to the regular tablet, and to be significantly more effective than desloratadine at reducing histamine-induced cutaneous wheals. A number of patient surveys demonstrated that the majority of individuals who tried the fast-dissolving formulation reported it to be convenient for use, fast-acting and preferred it to their previous antihistamine medication. Perhaps most importantly, a large proportion of patients indicated that they would prefer to use this new formulation in the future. Ebastine has a rapid onset of action and it can be administered once-daily, with or without food. Dose modifications are not needed in elderly patients, or in those with renal or mild to moderate hepatic impairment. Ebastine is generally well-tolerated, and clinical studies showed that at usual therapeutic doses of 10 and 20 mg once-daily, it had no clinically relevant adverse effects on cognitive function and psychomotor performance or on cardiovascular function. In conclusion, ebastine is an effective and generally well-tolerated treatment for allergic rhini

Topics: Animals; Butyrophenones; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Few randomized studies have compared the efficacy of ebastine and loratadine in the symptomatic treatment of seasonal allergic rhinitis (SAR).. A meta-analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group clinical trials comparing the efficacy of ebastine 20 mg once daily versus loratadine 10 mg once daily in the symptomatic treatment of SAR symptoms. Primary efficacy variable was the mean change in the overall mean daily reflective total symptom score (TSS), i.e. the sum of five rhinitis symptom scores: nasal discharge, nasal congestion, nasal itching, sneezing and total eye symptoms (itchy/watery eyes) over the first 2 weeks of treatment compared to baseline.. There were 2,089 patients in the population analyzed: 749, 739 and 601 patients in the ebastine 20 mg, loratadine 10 mg and placebo groups, respectively. Compared to baseline, overall mean daily reflective TSS over the first 2 weeks of treatment was -3.61 (35.4% reduction from baseline) in the ebastine group, -3.05 (29.0% reduction) in the loratadine group and -2.30 (22.7% reduction) in the placebo group. Statistically significant differences in the mean change from baseline were found when comparing ebastine and loratadine (p<0.001), ebastine and placebo (p<0.0001), and loratadine and placebo (p<0.0001). The global effect (i.e. the difference in overall mean daily reflective TSS over the first 2 weeks of treatment) of ebastine compared with loratadine over the first 2 weeks of treatment was -0.56 (95% confidence interval, CI, -0.86 to -0.26), and it was sustained during the whole (4-week) period studied. The global effects of ebastine and loratadine compared with placebo were -1.30 (95% CI, -1.61 to -0.99) and -0.74 (95% CI, -1.05 to -0.43), respectively. Secondary variables (reflective and snapshot individual symptom scores) showed the same trend.. This meta-analysis confirms that ebastine 20 mg has a good efficacy profile, inducing a greater decrease from baseline in mean rhinitis symptom scores than loratadine 10 mg or placebo.

Topics: Adult; Butyrophenones; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Multicenter Studies as Topic; Piperidines; Placebos; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.

Topics: Anti-Allergic Agents; Asthma; Butyrophenones; Clinical Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

We performed a systematic review of randomized, controlled trials to determine whether intranasal corticosteroids offered an advantage over topical antihistamines in the treatment of allergic rhinitis.. We searched for studies using MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical companies, and references of included trials.. Criteria for considering trials included: 1) published randomized controlled trials; 2) single- or double-blind studies; and 3) presence of one of the following clinical outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of life and side effects.. Nine studies including 648 subjects (mean age 30.4 years, range 13 to 73) with allergic rhinitis were selected. Intranasal corticosteroids produced significantly greater reduction of total nasal symptoms (standardized mean difference -0.36, 95% confidence interval -0.57 to -0.14), sneezing (-0.41, -0.57 to -0.24), rhinorrhea (-0.47, -0.64 to -0.29), itching (-0.38, -0.56 to -0.19), and nasal blockage (-0.86, -1.07 to -0.64) than did topical antihistamines. There was no significant difference between treatments for ocular symptoms (-0.07, -0.27 to 0.12). The effects on sneezing, rhinorrhea, itching, and ocular symptoms were significantly heterogeneous between studies. Other outcomes (total nasal symptom score and nasal blockage) were homogeneous between studies. Subgroup and sensitivity analysis suggested that most of the heterogeneity of outcomes could be explained on the basis of the methodologic quality of studies.. Intranasal corticosteroids produced greater relief of nasal symptoms than did topical antihistamines (topical H1 receptor antagonists). However, there was no difference in the relief of the ocular symptoms.

Topics: Administration, Intranasal; Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Middle Aged; Phthalazines; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Treatment Outcome

Oral antihistamines generally represent the first line of treatment (after allergen avoidance) in mild seasonal allergic rhinitis (SAR), and in perennial allergic rhinitis (PAR) where symptoms are intermittent. They are safe, effective and easily administered. First-generation antihistamines experienced problems mainly with sedation and anticholinergic activity. Second-generation antihistamines are safer and have largely eliminated these effects, although a very small number of patients taking terfenadine or astemizole have developed a characteristic ventricular dysrhythmia, 'torsade de pointes'. Ebastine is a potent second-generation H1-blocker that compares well with others in the class. It demonstrates no interaction with alcohol, does not induce sedation and has no clinically relevant effect on QTc interval at up to five times the maximum recommended dose. Ebastine acts rapidly to relieve symptoms of allergic rhinitis (including stuffiness) and has a long duration of action, allowing once-daily dosing. Whilst comparable in efficacy to other second-generation antihistamines at 10 mg, ebastine also has the advantage of flexible dosing. Thus, the lower dose of 10 mg is effective for treatment of mild SAR or PAR, and the dose can be increased to 20 mg once daily for control of patients with severe or chronic symptoms.

Topics: Butyrophenones; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Torsades de Pointes

Topics: Administration, Oral; Administration, Topical; Clinical Trials as Topic; Conjunctivitis, Allergic; Double-Blind Method; Histamine H1 Antagonists; Humans; Loratadine; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Terfenadine

Levocabastine is a potent and selective histamine H1-receptor antagonist which has been evaluated as a topical treatment (nasal spray and/or eyedrops) for allergic rhinitis and/or conjunctivitis. Data available at the time of the previous review in Drugs, together with more recent results, have clearly demonstrated that levocabastine nasal spray and eyedrops are clinically effective, have a rapid onset of action and are well tolerated in patients with nasal and/or ocular allergic conditions. Previous evidence indicating that topical levocabastine has efficacy similar to or better than that of topical sodium cromoglycate (cromolyn sodium) has been confirmed in more recent studies. Furthermore, results from a number of controlled clinical trials have also shown that topical levocabastine is at least as effective as oral terfenadine for the treatment of allergic rhinoconjunctivitis. Notably, topical levocabastine appears to be more effective than oral terfenadine in improving the severity of selected symptoms. Limited data indicating efficacy equivalent to that of oral loratadine, oral cetirizine or azelastine nasal spray will need to be confirmed. Data from several studies have shown that topical levocabastine has a tolerability profile similar to that of placebo, topical sodium cromoglycate or oral terfenadine. The main adverse events seen in patients treated with topical levocabastine are ocular irritation after application of eyedrops, and headache, nasal irritation, somnolence and fatigue after administration of the nasal spray. Administered doses of topical levocabastine, and subsequent plasma concentrations, are low, and the risk of systemic adverse events is therefore expected to be minimal. Thus, topical administration of levocabastine rapid and effective symptom relief with no apparent serious adverse events in patients with allergic rhinitis and/or conjunctivitis. Topical levocabastine is a useful alternative to topical sodium cromoglycate or oral terfenadine. Additional data supporting current evidence that topical levocabastine can provide more effective symptom relief than oral terfenadine, together with clarification of the relative efficacies of these agents in relation to varying pollen exposure, would help to further confirm its clinical potential. However, the results available to date suggest that the topical formulations of levocabastine are a valuable treatment option in patients with allergic rhinitis and/or conjunctivitis.

Topics: Aerosols; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal

Levocabastine is a novel H1-receptor antagonist for topical use, which is being investigated in allergic rhinitis (nasal spray) and conjunctivitis (eye drops). Its anti-allergic effects have been demonstrated in nasal and ocular provocation tests. Clinical studies have been performed in 1,363 patients with allergic rhinitis and 1,218 patients with allergic conjunctivitis, comparing levocabastine mainly to placebo and cromoglycate. Levocabastine was effective when used at a dose of 2 sprays per nostril or 1 drop per eye twice daily, which if necessary can be increased up to four times daily. Levocabastine was superior to placebo in alleviating symptoms such as sneezing, itchy nose, runny nose, itchy eyes, red eyes and lacrimation. In global evaluations some 60% of patients had good to excellent results with the nasal spray and some 75% with the eye drops. Levocabastine was shown to be as good or even slightly better than cromoglycate. Onset of action was fast, with 73% of patients reporting symptom relief within 30 min after administration of levocabastine nasal spray. Adverse experiences were similar in type and incidence with levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops. The most frequent complaints were nasal and ocular irritation, respectively, with a similar incidence for the three drugs. Limited data are available in children so far, but they indicate response rate and adverse-experience profile to be similar to what was observed in adults. Levocabastine, thus, is an interesting new antihistamine available for topical use in allergic rhinoconjunctivitis. It has been extensively evaluated in adults, and preliminary data indicate that it can also be useful in allergic children.

Topics: Administration, Intranasal; Animals; Child; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Nasal Provocation Tests; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The new H1-receptor antagonist levocabastine is the most potent antihistamine available, as shown in classical animal tests for antihistamine activity. Its effects also are very specific, with doses as high as 40,000 times the effective antihistamine dose not displaying other pharmacological effects. In nasal and ocular provocation tests, levocabastine nasal spray and eye drops protected against allergen-induced nasal and ocular symptoms. Twenty-three clinical trials have been performed with levocabastine nasal spray in 1363 patients with allergic rhinitis. At a dose of two sprays per nostril twice daily (if necessary to be increased up to four times daily), levocabastine was significantly better than placebo and as good as or slightly better than cromoglycate in alleviating nasal symptoms. Good to excellent results were reported in about 60% of patients on levocabastine, compared with 37% with placebo and 47% with cromoglycate. Levocabastine eye drops were studied in 21 clinical trials including 1218 patients with allergic conjunctivitis. One drop per eye twice daily (up to four times daily) provided significantly better symptom control than placebo and similar effects as those observed with cromoglycate. Response rates were 71-80% with levocabastine, 55% with placebo and 76% with cromoglycate. Levocabastine has a fast onset of action, with 94% of patients experiencing symptom relief within 15 min after the first instillation of levocabastine eye drops. Three long-term studies (10-16 weeks' duration) showed absence of tachyphylaxis during prolonged treatment with levocabastine. The incidence of adverse experiences was similar for levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The clinical manifestations of allergic rhinitis are the result of an immune-mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate alpha-adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen-induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell-stabilizing agent nedocromil sodium, the anticholinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Glucocorticoids; Histamine H1 Antagonists; Humans; Ipratropium; Nedocromil; Piperidines; Pregnenediones; Quinolones; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Anti-Allergic Agents; Butyrophenones; Double-Blind Method; Drug Therapy, Combination; Histamine H1 Antagonists; Humans; Mometasone Furoate; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal

Toll-like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development.. Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035.. This randomized, double-blind, placebo-controlled study (TL7116958) was conducted over two pollen seasons (2013-2014) and follow-up study (204509) conducted 1 year later. Participants with allergic rhinitis (n=42) were randomized to receive eight weekly doses of i.n. GSK2245035 (20 ng [2014 Cohort; n=14] or 80 ng [2013 Cohort; n=14]) or placebo (n=14). Adverse events (AEs) including cytokine release syndrome AEs (CytoRS-AEs) and nasal symptoms were assessed. Nasal and serum IFN-inducible protein 10 (IP-10) were measured after doses 1 and 8, then 1 (follow-up visit [FUV] 1) and 3 (FUV2) weeks after final dose. Nasal allergen challenges (NACs) and allergic biomarker assessment (nasal, serum) were conducted at baseline, FUV1, FUV2 and at a FUV 1 year after final dose (FUV3; 2014 Cohort only). A Bayesian framework enabled probability statements for mean effect sizes.. GSK2245035 induced CytoRS-AEs (most commonly headache, median duration <1 day) in 93% of participants at 80 ng, while AE incidence at 20 ng was similar to placebo. There was no evidence of nasal inflammation. Dose-related increases in nasal and serum IP-10 were observed 24 hours after doses 1 and 8 (>95% certainty). Both doses showed a trend in reducing total nasal symptom score 15 minutes post-NAC at FUV1 and FUV2, but there was no reduction evident at FUV3. Nasal levels of selected allergic biomarkers demonstrated trends for reductions at FUV1, FUV2 and FUV3.. Weekly i.n. GSK2245035 20 ng was well tolerated and reduced allergic reactivity to nasal challenge for 3 weeks post-treatment.

Topics: Adenine; Administration, Intranasal; Adult; Aged; Allergens; Biomarkers; Drug Monitoring; Female; Follow-Up Studies; Humans; Immunization; Male; Middle Aged; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Seasons; Toll-Like Receptor 7; Treatment Outcome; Young Adult

Bilastine, a novel non-sedating second-generation H. This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13).. A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated.. After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

Topics: Adult; Asian People; Benzimidazoles; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

Environmental exposure chambers have been used to expose subjects to aeroallergens to investigate the efficacy of prophylactic treatment with symptomatic agents in Japan. We first examined the therapeutic effect of bilastine (BIL), a novel non-sedative second-generation H. This was a randomized, double-blind, four-way crossover, placebo- and active-controlled phase II study (trial registration number JapicCTI-132213). Subjects were exposed to cedar pollen (8000 grains/m. We enrolled 136 subjects and the sum of TNSS on Day 1 of the three active treatments was significantly lower than that of placebo and was maintained up to 26 h after the first dosing (Day 2). The sum of TNSS or sneezing score on Day 1 after BIL 20 mg was more significantly decreased than after FEX. Moreover, BIL showed a faster onset of action than FEX.. We demonstrated the efficacy, rapid onset, and long duration of action of BIL in subjects with Japanese cedar pollinosis exposed to cedar pollen using the OHIO Chamber.

Topics: Adult; Benzimidazoles; Cryptomeria; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR).. Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements.. Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR.. Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

Topics: Adult; Benzimidazoles; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

To compare the onset of action, efficacy, and safety of azelastine and levocabastine in the treatment of allergic rhinitis.. In a multicenter, randomized, double-blind, parallel-group trial, 244 patients with moderate-to-severe allergic rhinitis were randomized to receive either azelastine hydrochloride nasal spray (ANS) 0.1% or levocabastine hydrochloride nasal spray (LNS) 0.05% for 14 consecutive days. A visual analog scale was used to record total nasal symptom score (TNSS) changes. Indexes for further assessment included onset of action, total effective rate, and evaluation of therapeutic effect.. Statistically significant changes from baseline in TNSS were seen in both the LNS group and the ANS group. No significant differences were seen between the two groups in terms of evaluation of therapeutic effect, total effective rate, and onset of action, except for a higher symptom relief rate in the LNS group than in the ANS group within 30 min of administering the first dose. Adverse reactions were mild to moderate, with an incidence of 0.9% for LNS and 2.5% for ANS.. Both ANS and LNS were effective and safe in the treatment of moderate-to-severe persistent allergic rhinitis. Moreover, LNS reached a higher symptom relief rate within 30 min of administering the first dose.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Nasal Sprays; Phthalazines; Piperidines; Retrospective Studies; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome; Young Adult

This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis.. 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.. 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.

Topics: Adolescent; Adult; Allergens; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Cross-Over Studies; Double-Blind Method; Eye Diseases; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Nasal Mucosa; Nose Diseases; Ophthalmic Solutions; Piperidines; Placebos; Rhinitis, Allergic, Seasonal; Terfenadine

Bilastine is a novel, nonsedating H(1)-antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR).. This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12-70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period.. Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%).. Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms.

Topics: Adolescent; Adult; Aged; Area Under Curve; Benzimidazoles; Child; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Loratadine; Male; Middle Aged; Piperidines; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome; Young Adult

To investigate the efficacy and safety of bepotastine, we conducted a randomized, investigator-blind, placebo-controlled and parallel study to evaluate the allergic symptoms and the cognitive function of the subjects with Japanese cedar (JC) pollinosis in response to JC pollen exposure in an artificial exposure chamber.. Twenty-four volunteers with JC pollinosis were enrolled in this study. The subjects were randomly divided into two groups: a bepotastine group and a placebo group (12 subjects each). Subjects received either a 10-mg bepotastine OD (orally disintegrating) tablet or a placebo 10 min before entering the chamber for a 3-h exposure. The nasal and ocular symptoms were evaluated by each patient at regular intervals. The amount of nasal discharge was measured and the number of sneezes recorded. To evaluate the cognitive function, a digit cancellation test (D-CAT), in which the subjects have to eliminate certain numbers within a fixed time, was conducted.. Twelve subjects in the placebo group developed nasal and/or ocular symptoms, whereas six subjects in the bepotastine group showed none of the symptoms during exposure. Mean secretion weights and number of sneezes were significantly lower in the bepotastine group than in the placebo group. In D-CAT, no deterioration of work performance was observed in the bepotastine group. No adverse effects were observed in either group.. Bepotastine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to JC pollen in an exposure chamber.

Topics: Administration, Oral; Air Pollutants; Allergens; Anti-Allergic Agents; Atmosphere Exposure Chambers; Cognition; Female; Humans; Male; Nasal Lavage Fluid; Nasal Mucosa; Piperidines; Pollen; Pyridines; Rhinitis, Allergic, Seasonal; Single-Blind Method; Tablets

Guidelines for allergic rhinitis are more effective than free-treatment choice in the control of seasonal allergic rhinitis.. To validate the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines in the treatment of intermittent and persistent allergic rhinitis induced by pollens.. A multicenter, open-label, parallel, pragmatic randomized study compared two therapeutic strategies during a 2-week treatment course. In the first strategy ('guidelines group'), 417 patients were treated according to ARIA with ebastine as oral antihistamine. In the second strategy ('free-choice treatment group'), investigators had a free choice for the treatment of 422 patients.. Quality of life measured using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), work productivity and daily symptom medication scores.. 94.2% patients returned the baseline visit questionnaires and 88.6% returned the posttreatment period questionnaires. RQLQ scores were similar in the two groups at baseline. After treatment, there were improvements in the overall score and in all domains in both treatment groups. According to pragmatic methodology, the improvements show that the guidelines group (-1.70 +/- 1.20) is more effective than the free-choice treatment group (-1.52 +/- 1.22) with a gamma risk of 2%. Individual RQLQ scores, work productivity, and daily symptom scores were significantly improved in the guidelines group by comparison to the free-choice treatment group.. A treatment based on ARIA guidelines offers patients a significant improvement in comparison to the use of a nonstandardized treatment regimen.

Topics: Adolescent; Adult; Butyrophenones; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality of Life; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Young Adult

Bilastine is a new non-sedative H(1) receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial).. To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR).. Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms.. The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively).. Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Cetirizine; Child; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Receptors, Histamine H1; Rhinitis, Allergic, Seasonal; Time Factors

The guidelines of German and European associations of allergology recommend the treatment of severe allergic rhinitis with a combination of oral antihistamines and nasal steroids. Many patients face this option rather skeptically, so that ENT specialists mostly use antihistamine monotherapy with a higher dosage. This increased dose may cause drowsiness, as has been demonstrated for cetirizine and loratadine. However, ebastine is a non-sedating antihistamine. Furthermore, it has been shown that improved clinical efficacy can be attained with an increased dosage of 20 mg daily in comparison to the usual dosage of 10 mg/day without increasing the rate of side effects.. In this prospective post-marketing survey, the treatment of 4,307 patients with allergic rhinitis was documented during the pollen season 2005. The severity of rhinitis symptoms and satisfaction with the treatment were recorded.. Treatment with 20 mg ebastine daily as monotherapy led to a significantly greater reduction in symptoms (P=0.002) than the combination therapy.. This outcome could be attributed to an assumed better compliance in patients with monotherapy.

Topics: Adrenal Cortex Hormones; Adult; Butyrophenones; Conjunctivitis; Drug Combinations; Female; Germany; Histamine H1 Antagonists; Humans; Male; Piperidines; Practice Patterns, Physicians'; Prevalence; Rhinitis, Allergic, Seasonal; Treatment Outcome

Approximately 16.2% of the Japanese population suffer from cedar pollinosis, with various manifestations such as ophthalmic, laryngo-pharyngeal and skin symptoms in addition to nasal symptoms. Thus, the annual pollen season is an agonizing period for patients. No study has reported symptoms and their clinical courses after conjunctival provocation with purified cedar pollen allergen Cry j1 as well as suppression of these allergen-induced ocular symptoms by antihistamine eye drops.. Nine patients with Japanese cedar pollinosis who had no nasal or ocular symptoms were included in the present study, after obtaining informed consent in writing. 1) Purified cedar pollen allergen Cry j1 was instilled in the left eye and phosphate-buffered saline (PBS) in the right eye as a control. 2) Levocabastine hydrochloride ophthalmic suspension and ketotifen fumarate ophthalmic solution were respectively instilled in the left and right eyes, which were then challenged with the allergen. Ocular symptoms after provocation with the allergen were recorded through the clinical course.. Pollen allergen-induced ocular symptoms were itching and hyperemia of the palpebral conjunctiva, and itching lasted for more than 5 hours. Moreover, preadministration of antihistamine eye drops suppressed the increases in the ocular symptom scores, eliminating itching within 1 hour. Allergen provoked not only ocular symptoms but also nasal symptoms in 77.8% of patients.. Preadministration of antihistamine eye drops suppressed the symptoms induced by the allergen, which suggests that this is an effective early therapy for Japanese cedar pollinosis, if it is started before the pollen season. However, self-protection by patients using a mask may not be effective enough to suppress nasal symptoms during the pollen season, requiring them to additionally wear glasses to avoid exposure to the allergen.

Topics: Adult; Allergens; Antigens, Plant; Conjunctivitis, Allergic; Cryptomeria; Dose-Response Relationship, Immunologic; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hyperemia; Japan; Ketotifen; Ophthalmic Solutions; Piperidines; Plant Proteins; Pollen; Premedication; Pruritus; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

Drug treatment and specific immunotherapy (SIT) are both effective in seasonal rhinoconjunctivitis, but the former acts only on allergic symptoms while the latter modifies the natural history of the disease. Only a few studies compared the clinical efficacy of the two treatments with contrasting results. We planned a study to compare the efficacy of SIT (15 patients) and drug treatment (15 patients) in moderate to severe seasonal rhinoconjunctivitis caused by sensitization to grass pollen. SIT was performed by a 5-grass extract standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergénes, Antony, France) using the conventional build-up phase in 12 weeks and a maintenance treatment with monthly injection for three years. Drug treatment was done with cetirizine as antihistamine, mometasone furoate as nasal topical steroid, and levocabastine eyedrops. All patients registered during the pollen season their symptoms and drug consumption. After one year 12 of 15 patients treated with SIT had less symptoms and drug consumption in respect to baseline compared to none in drug treated group (p = 0.021) and after three years 15 of 15 were improved in group A compared to one of 15 in group B (p = 0.008). These findings indicate an higher efficacy of SIT in patients with seasonal rhinitis not only in the long term but also in the first year of treatment.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Anti-Allergic Agents; Anti-Inflammatory Agents; Cetirizine; Conjunctivitis, Allergic; Desensitization, Immunologic; Drug Therapy, Combination; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Mometasone Furoate; Ophthalmic Solutions; Piperidines; Poaceae; Pollen; Pregnadienediols; Rhinitis, Allergic, Seasonal; Treatment Outcome

Current guidelines recommend intranasal glucocorticosteroids as first-line therapy for seasonal allergic rhinitis.. To compare the efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid mometasone furoate, the topical antihistamine levocabastine hydrochloride, and the cromone disodium cromoglycate in seasonal allergic rhinitis.. This study was performed during the 2003 grass pollen season as an open, randomized, parallel-group, single-center study of 123 patients assigned to receive mometasone furoate (200 microg once daily), levocabastine hydrochloride (200 microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom scores and nasal inspiratory peak flow measurements were recorded in a patient diary. The global efficacy of the study medication was evaluated by patients after treatment. Eosinophil cationic protein concentrations were measured in nasal secretions before and after treatment. Cost-effectiveness was evaluated as medication cost per treatment success.. Mometasone furoate therapy was significantly superior to the use of levocabastine or disodium cromoglycate with respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil cationic protein concentration. Furthermore, mometasone furoate therapy was significantly superior to disodium cromoglycate therapy with respect to nasal inspiratory peak flow. Medication cost per treatment success was lowest with mometasone furoate use and highest with levocabastine use.. This is the first study to compare mometasone furoate nasal spray with nonsteroidal topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray was confirmed as a first-choice topical treatment option for seasonal allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Allergic Agents; Cromolyn Sodium; Eosinophil Cationic Protein; Female; Humans; Male; Middle Aged; Mometasone Furoate; Piperidines; Pregnadienediols; Respiratory Function Tests; Rhinitis, Allergic, Seasonal; Treatment Outcome

Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity.. The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens.. This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8).. Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects.. In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated.

Topics: Adolescent; Adult; Aged; Child; Conjunctivitis, Allergic; Dibenzazepines; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal

Few randomized studies have compared loratadine to ebastine in the symptomatic treatment of seasonal allergic rhinitis (SAR) patients.. This double-blind, placebo-controlled, randomized, parallel-group, comparative trial compared the efficacy and safety of ebastine 20 mg (E20), loratadine 10 mg (L10) and placebo (P), administered once daily, in the control of SAR symptoms over a 2-week period. An additional 2-week treatment period was included in order to check sustained efficacy and tolerability.. A total of 703 patients were enrolled: 282 patients in the E20 group, 279 in the L10 group and 142 in the P group. E20 showed a greater decrease from baseline in the main efficacy variable (mean daily reflective total symptom score) than L10 (p = 0.0018) or P (p = 0.0024), whereas the difference between L10 and P was not significant. Moreover, reductions from baseline in all composite/individual daily reflective rhinitis symptom scores were significantly larger in patients receiving E20 than in patients receiving L10 or P. Most significant differences between E20 and L10 or P were maintained after 4 weeks of treatment. Overall, all treatments were safe and well tolerated. There was no significant difference in the percentage of patients who reported one or more adverse events (AEs) between the groups, and most AEs were mild to moderate (89.9%).. E20 given once daily for 2 weeks was more effective in the treatment of SAR symptoms than L10 or P. E20 also showed a sustained efficacy after 4 weeks of treatment, and overall was well tolerated and proved safe.

Topics: Adolescent; Adult; Aged; Butyrophenones; Child; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Least-Squares Analysis; Loratadine; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

Few randomized studies have compared the H1-receptor antagonists loratadine and ebastine in seasonal allergic rhinitis (SAR) patients. The objective of this study was to compare the efficacy and safety of ebastine 20 mg (E20), ebastine 10 mg (E10), loratadine 10 mg (L10), and placebo (P), once daily, in controlling symptoms of SAR over a 4-week period. This was a double-blind, placebo-controlled, randomized, parallel-group study. Efficacy was assessed in 749 patients (12 to 70 years old) by SAR symptom scores (nasal discharge, congestion, itching, sneezing, and total eye symptoms) entered on diary cards every morning and every evening over the previous 12 hours (reflective score) and at the time of recording (snapshot score). The E20 group showed greater reductions from baseline compared with the L10 group in 2 daily reflective composite scores (nasal index [with or without congestion]) and in all 4 daily snapshot composite scores. E10 and L10 groups showed no significant differences in either the daily reflective or snapshot scores overall although E10 showed a greater improvement of nasal discharge snapshot score than L10. The efficacy of E20 at controlling the symptoms of SAR was well sustained during the fourth week of treatment, with significant differences over placebo in 22/36 total rhinitis symptom scores, followed by E10 (6/36), whereas L10 showed no differences (0/36). Patient and physician global evaluations at the final visit were not statistically significant for any treatment group compared with placebo. There was no significant difference among all groups in the number of patients who reported adverse events. In conclusion, ebastine 20 mg given once daily for 4 weeks in the treatment of SAR showed larger mean reductions from baseline in most rhinitis symptoms scores than loratadine 10 mg. Sustained efficacy was most frequently observed with ebastine 20 mg over placebo, whereas loratadine 10 mg did not provide a statistically significant improvement in any individual or composite symptom score at the end of the fourth week. Both ebastine 20 and 10 mg were well tolerated and proved safe in the treatment of SAR.

Topics: Administration, Oral; Butyrophenones; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Loratadine; Male; Multivariate Analysis; Patch Tests; Piperidines; Probability; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

The aim of this study is to establish the efficacy and safety of rupatadine vs ebastine and placebo in the treatment of seasonal allergic rhinitis (SAR). Rupatadine is a new second generation H(1)-antihistamine with once-daily dosing that may provide better control of symptoms than the currently used H(1)-receptor blockers because of its dual pharmacological profile (anti-PAF and anti-H(1)).. In a multicentre study, 250 patients with SAR were included in a double-blind, randomized, parallel-group and placebo-controlled study. Patients received either rupatadine 10 mg, ebastine 10 mg or placebo once daily for 2 weeks. The main efficacy outcome was based on the patient's record of severity of nasal symptoms (sneezing, nasal itching, runny nose and nasal obstruction) and nonnasal symptoms (conjunctival itching, tearing and pharyngeal itching). The daily total symptom score (DTSS) was the mean of the DSS recorded for each of the seven symptoms assessed, and the mean DTSS (mDTSS) was the mean of the DTSS values for each study day.. Significant differences in mDTSS were detected between rupatadine and placebo (33% lower for rupatadine group; P = 0.005) after 2 weeks of treatment. The TSS for rupatadine were 22% lower than for ebastine, although the differences were not statistically significant. No serious adverse events were reported during the study period.. Rupatadine 10 mg once daily was clearly superior to placebo in alleviating the symptoms of SAR over a 2-week period. In comparison with ebastine, rupatadine shows a trend towards a better profile as regard several secondary efficacy variables.

Topics: Adolescent; Adult; Analysis of Variance; Anti-Allergic Agents; Butyrophenones; Cyproheptadine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

Three similarly designed, multicenter, double-blind, randomized, placebo-controlled, parallel-group comparative studies were carried out in the United States in a total of 1,881 patients to evaluate the efficacy of ebastine 20 mg (E20), ebastine 10 mg (E10), loratadine 10 mg (L10), and placebo (P), all given once daily, in controlling the symptoms of ragweed-induced rhinitis over a 4-week treatment period. Efficacy was assessed, among other means, by nasal congestion symptom scores entered by patients on diary cards in the morning and before bedtime over the previous 12-h period (reflective score, R) and at the time of recording (snapshot score, SS). Mean value of both morning and evening score changes from baseline were analyzed in each study and for each treatment. E20 was more effective than placebo in all studies, in both R and SS symptom scores (6 of 6 scores), while E10 was effective in 4 of 6 scores (2 R and 2 SS). In contrast, L10 was effective in only 1 of 6 scores (1 R). In conclusion, the comparative analysis of the results from these three trials shows that ebastine is efficacious in the reduction of nasal congestion associated with seasonal allergic rhinitis. This symptomatic effect of ebastine may be accounted for by its ability to reduce inflammatory markers, as shown in preclinical studies, in addition to its primary effect of antagonizing histamine H1 receptors.

Topics: Adult; Ambrosia; Butyrophenones; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Nasal Obstruction; Piperidines; Rhinitis, Allergic, Seasonal

Allergic rhinitis is a common disease altering quality of life. Its treatment is well established and guidelines have been proposed. However, their efficacy has never been tested. The aim of the study was to validate the guidelines of the International Consensus on Rhinitis in the treatment of seasonal allergic rhinitis.. A multicenter, multinational, open label, parallel, randomized study compared two therapeutic strategies in seasonal allergic rhinitis during a 3-week treatment. General practitioners were randomized into two groups. In the first group of 224 patients, doctors followed guidelines from the International Consensus on Rhinitis. Depending on the severity of nasal and ocular symptoms defined using visual analogue scales, patients received ebastine (an oral antihistamine), triamcinolone acetonide (a topical corticosteroid) and/or ophthalmic nedocromil sodium (a topical ocular cromone). In the second group of 241 patients, general practitioners had a free choice of treatment. The primary efficacy end points were quality of life measured using the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ) and the symptom-medication scores assessed daily with an electronic dairy system.. Adjusted mean total symptom scores over 21 days were 4.93 in the guidelines strategy group compared with 7.48 in the free-choice treatment group (P = 0.0001). Mean total scores in the RQLQ decreased by 2.19 in the guidelines group compared with a decrease of 1.79 in the free-choice treatment group (P = 0.0001). At 21 days, the least square mean difference in improvement in overall scores for RQLQ in the guidelines group compared with the free-choice treatment group was 0.53, which was greater than the minimal important difference.. Patients with seasonal allergic rhinitis often present severe symptoms which are not well recognized or controlled by physicians using their own criteria of severity and treatment. Using a simple method for the evaluation of the severity and a simple therapeutic scheme based on International Guidelines, patients with seasonal allergic rhinitis presented a significant improvement by comparison with those receiving a non-standardized treatment.

Topics: Administration, Intranasal; Administration, Oral; Adult; Anti-Allergic Agents; Butyrophenones; Conjunctivitis, Allergic; Female; Glucocorticoids; Guideline Adherence; Histamine H1 Antagonists; Humans; Male; Nedocromil; Piperidines; Practice Guidelines as Topic; Quality of Life; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Triamcinolone Acetonide

The efficacy and safety of ebastine 20 mg once daily given with and without food were compared in patients ages 12 to 70 years with seasonal allergic rhinitis (SAR) caused by mountain cedar allergen. This double-blind, placebo-controlled study was conducted at six centers in Texas. Efficacy and safety analyses were performed on the intent-to-treat population, which comprised 652 patients; 540 patients completed the study. Following 2 weeks' treatment, no significant differences (p > or = 0.91) were found between the ebastine with and without food groups in the percentage change from baseline of daily "reflective" total rhinitis symptom scores (i.e., patients' assessment of severity over the previous 12 h), but both ebastine groups exhibited significantly greater reductions versus patients receiving placebo (p < 0.0001). There were also no significant differences in the percentages of patients experiencing adverse events between the ebastine with and without food groups. Mean steady-state plasma concentrations of ebastine and its active metabolite carebastine were, respectively, 5.5% (ns) and 15.1% (p < 0.05) higher when ebastine was given with food versus its administration without food. Overall, these results indicate that in clinical practice, ebastine does not need to be administered with reference to food.

Topics: Adolescent; Adult; Aged; Butyrophenones; Child; Double-Blind Method; Female; Food-Drug Interactions; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

Placebo-controlled outdoors clinical study was performed at the Utsunomiya City Forest Park surrounded by many cryptomerias on March 5, 2000, at the season of most cedar pollens, to evaluate the efficacy and its timing and duration of Ebastine. It was a fine weather on the day of the study, and so much cedar pollens as 235 pollens/cm2 were spreading at the park when it was measured at the park. In particular, the amount of cedar pollen for 2 hours from 10:00 a.m. when Ebastine was administered exceeded 50 pollens/cm2 per hour. The nasal symptoms of the placebo-treated subjects promptly aggravated during the time, while the symptoms of the subjects who received oral Ebastine showed the tendency to improve from 2 hours after oral administration under exposure of a large amount of cedar pollens, and the efficacy maintained until 10:00 a.m. at the next morning that passed 24 hours after administration. The results suggest that Ebastine promptly inhibited the symptom induced by the exposure of a large amount of pollens at the season of most cedar pollens and that once daily oral administration of Ebastine maintained the efficacy at least for 24 hours. It was also suggested that outdoors comparative clinical study at the season of cedar pollen was effective to observe and evaluate the natural clinical course of a patient's symptom and was useful for evaluation of clinical efficacy of anti-pollinosis drugs of various types, including an anti-allergic reagent.

Topics: Adult; Butyrophenones; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Pollen; Rhinitis, Allergic, Seasonal; Single-Blind Method

The aim of the present investigation was to compare the efficacy and tolerability of azelastine (CAS 58581-89-8) (1.12 mg/day) and levocabastine (CAS 79547-78-7) (0.4 mg/day) nasal spray administered twice daily to patients with seasonal allergic rhinitis. A total of 180 patients participated in a 4-week, double-blind, parallel group (n = 90 each) study. Symptom severity of nasal, ocular and other symptoms were recorded, out of which a total symptom score (TSS) was calculated. Physicians assessed symptoms at baseline and at days 7, 14, and 28, patients and physicians evaluated the efficacy and tolerability. After 4 weeks of treatment with azelastine the mean overall TSS was reduced from a baseline score of 18.7 to 4.2, after levocabastine from 17.8 to 5.9. Patients morning scores for treatment days 1 to 28 gave a mean total score of 212.4 for the azelastine group and 230.6 for the levocabastine group; the equivalent evening scores yielded a mean total score of 115.5 and 175.6 respectively. Global efficacy was judged by physicians as either 'very good' or 'good' for 90% of azelastine patients and for 74% of the levocabastine group; 92% of azelastine patients and 76% of levocabastine patients judged treatment to be either 'very good' or 'good'. No serious adverse events were reported, all adverse events were related to nasal symptoms. Both azelastine and levocabastine administered twice daily as a nasal spray provide effective and well tolerated symptomatic treatment of seasonal allergic rhinitis. Azelastine, however, was statistically superior in efficacy as well as in safety (PWei-Lachin < 0.0001, combined results).

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Anti-Allergic Agents; Double-Blind Method; Endpoint Determination; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Phthalazines; Piperidines; Rhinitis, Allergic, Seasonal; Risk Assessment

Ebastine and loratadine are 2 nonsedating second-generation H(1) antihistamines with once-daily dosing.. We compared the efficacy and safety of ebastine 20 mg and 10 mg, loratadine 10 mg, and placebo administered once daily for 4 weeks in controlling the symptoms of seasonal allergic rhinitis (SAR).. In a double-blind, placebo-controlled, randomized, parallel-group study, 565 patients with ragweed SAR, ages 12 to 70 years, received either ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, or placebo once daily for 4 weeks. Patients recorded morning and evening reflective scores (past 12 hours) as well as snapshot scores (at time of recording) for nasal discharge, congestion, sneezing, itching, and total eye symptoms. Total symptom score (TSS) is the sum of these 5 scores.. Ebastine 20 mg produced significantly greater (P <.05) reductions from baseline compared with loratadine 10 mg over the entire treatment period in the mean daily reflective (42.5% vs 36.3%) and mean morning snapshot (40.3% vs 31.3%) TSS. The overall improvement in daily reflective and morning snapshot TSS was comparable between ebastine 10 mg and loratadine 10 mg and significantly better than placebo (P <.05). The total percent of patients with adverse events was similar among all 4 treatment groups (P =.78).. Ebastine 20 mg given once daily was significantly superior to loratadine 10 mg given once daily at improving the rhinitis total symptom score throughout the day and at awakening over a 4-week period. Ebastine 20 mg and 10 mg doses were both efficacious and well tolerated in the treatment of SAR.

Topics: Adolescent; Adult; Aged; Butyrophenones; Child; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

Although prior studies have documented the rapid onset of action of topical intranasal levocabastine (LEV), little is known about its duration of action under nasal challenge conditions.. We sought to assess the onset and duration of action of escalating doses of LEV nasal spray by using a nasal allergen challenge (NAC) model.. Eighteen asymptomatic subjects with histories of seasonal allergic rhinitis were enrolled into a randomized, single-blind, placebo-controlled, dose-ranging crossover study. Each patient was randomly assigned to receive single doses of placebo and intranasal LEV 0.1, 0.2, and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC consisted of a single dose of allergen administered 5 minutes after study drug treatment. In part 2 (duration of action), NAC consisted of increasing doses of allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were measured after NAC in both phases of the study. Blood samples for plasma LEV concentrations were drawn after each NAC.. In part 1, NSSs were significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared with placebo (P <.05). In part 2, NSSs were significantly lower after LEV doses of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after treatment (P <.05). The mean provocative dose of allergen required to elicit a positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5, 6, and 12 hours after treatment. Nasal peak expiratory flow rates demonstrated no significant differences between LEV and placebo for any doses at any time points. Mean plasma LEV concentrations were low (range, 0 to 3. 7 ng/mL) after all doses and did not correlate with drug efficacy.. Single intranasal LEV doses of 0.1, 0.2, and 0.4 mg significantly reduced the severity of the immediate nasal response to allergen when administered 5 minutes before NAC. This protective effect against NAC continued to be present 24 hours after administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory effect was due largely to topical rather than systemic effects.

Topics: Administration, Intranasal; Adult; Allergens; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Provocation Tests; Piperidines; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Single-Blind Method; Trees

Treatment options for allergic rhinitis include antihistamines, decongestants, anticholinergics, cromolyn sodium and corticosteroids. As the nose is a small organ, comprising less than 1% of total body mass and surface area, it seems logical to confine treatment of rhinitis to the diseased organ.. To evaluate the effects of therapy with intranasal fluticasone propionate (FP), both on subjective symptoms and pathophysiological mechanisms, in rhinitis patients during pollen season when the patients were symptomatic.. We used a double-blind, placebo (PLA)-controlled, randomized, double dummy, parallel group study of the effect of 6 weeks treatment. The double-blind comparison was made between the following three treatments: FP aqueous nasal spray, 200 microg taken once daily, levocabastine (LEV) nasal spray, 200 microg taken twice daily and PLA nasal spray. Clinical evaluation and the levels of cells and mediators in nasal washing were performed before and after treatments. Twenty-four patients (11 men and 13 women, aged 17-50 years, mean age 30.1 +/- 8.5) with strictly seasonal allergic rhinitis to Parietaria entered the study. Clinical evaluation and the levels of inflammatory cells (eosinophils and activated eosinophils, i.e. EG2+) and their mediators (tryptase, eosinophil cationic protein, eosinophil protein X and neutrophil myeloperoxidase) in nasal-lavage were performed before and after treatments.. Treatment with FP significantly increased, with respect to placebo, the percentage of days without sneezing (P < 0. 001), nasal blockage (P < 0.001), rhinorrhea (P < 0.001), nasal itching (P < 0.001). Furthermore, treatment with FP showed additional benefits with respect to LEV. The percentage of days without nasal blockage was significantly higher in the FP group that in the placebo group (P = 0.018). The same applied to rhinorrhea (P = 0.009). The percentages of days without sneezing and itching were instead not significantly different between the two groups. As expected, no significant differences were observed in baseline medians of the rhinitis symptom scores as well as in mean values of all mediators and eosinophils in nasal lavages of the various groups under study. After treatment the mean of subjective symptoms as well as all values in nasal lavage level fell significantly only in the FP group, whereas no significant changes were observed either in LEV or PLA groups. Accordingly, significant differences were observed at the end of the treatments between the values of fluticasone group vs LEV and PLA group values. Significant correlations between these values and symptom scores were found, according with literature data suggesting a pathogenetic role for these mediators and eosinophils in rhinitis.. FP (200 microg once daily) affords a significant degree of improvement in rhinitis control during pollen season, as measured by subjective and objective parameters, compared with LEV (200 microg twice daily) and PLA. The therapeutic benefits of intranasal FP are reflected in, and may be caused by, the decrease in nasal inflammatory cells.

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Piperidines; Pollen; Rhinitis, Allergic, Seasonal

Ebastine is a nonsedating and selective histamine H1 receptor antagonist without anticholinergic or sedative effects at therapeutic doses. It has shown a rapid onset and long duration of action, and doses of 10 and 20mg once daily are effective in relieving the nasal and non-nasal symptoms of seasonal and perennial allergic rhinitis (SAR and PAR, respectively). In 3 randomised double-blind, multicentre clinical trials in patients with SAR, ebastine 10 and 20mg once daily for 2 to 3 weeks significantly reduced symptoms (nasal discharge, stuffiness, sneezing, itchy nose, itchy/watery eyes) when compared with placebo. Similarly, in patients with PAR, two 3-week studies demonstrated that ebastine 10mg twice daily and 20mg once daily significantly relieved the symptoms of PAR, as measured by the Perennial Index. Ebastine was well tolerated in these studies and had no effect on the QTc interval.

Topics: Adolescent; Adult; Aged; Butyrophenones; Child; Double-Blind Method; Electrocardiography; Electrocardiography, Ambulatory; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Eosinophilia; Female; Fluticasone; Histamine H1 Antagonists; Humans; Hydrocortisone; Male; Piperidines; Rhinitis, Allergic, Seasonal

This study compares the effects of two topical nasal treatments for allergic rhinitis, budesonide and levocabastine, on symptom development during seasonal pollen exposure. Additionally, the protective effects of drug treatments on allergen-challenge-induced responses (symptoms and microvascular exudation of plasma) are examined late into the pollen season. Forty-four patients with seasonal allergic rhinitis to birch pollen participated in this single-blind, randomized, and placebo-controlled study. Topical nasal treatment with either levocabastine (200 microg b.i.d.; n = 16), budesonide (200 microg b.i.d.; n = 16), or placebo (n = 12) was instituted before the start of the pollen season and continued for 5 weeks until the end of the birch pollen season. The participants kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges with increasing doses of a birch pollen extract (10[2], 10[3], and 10[4] SQ-U) were carried out both before, when patients were asymptomatic and without treatment, and late into the pollen season. A nasal lavage followed each challenge, and the lavage fluid levels of albumin were measured as an index of the acute inflammatory response of the allergic mucosa. The birch pollen season was rather mild, producing only small increases in nasal symptoms. Budesonide treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to levocabastine (P<0.05), while levocabastine treatment did not differ significantly from placebo. Ocular symptoms and use of rescue medication did not differ between placebo and the active treatments. At the end of the pollen season, both treatments reduced allergen-challenge-induced nasal symptoms compared to placebo (P<0.01). Only budesonide reduced allergen-challenge-induced increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in comparison with placebo). The results suggest that budesonide reduces both seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is effective against allergen-challenge-induced symptoms also during the season. In addition, the topical steroid treatment, but not the antihistamine, inhibits the inflammatory exudation evoked by allergen challenge in patients with active seasonal disease.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Budesonide; Capillary Permeability; Female; Glucocorticoids; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Single-Blind Method

In a randomised, multicentre study, the effect of azelastine eye drops (n = 51 patients) was compared in a double-blind manner with placebo eye drops (n = 30 patients) and in an open manner with levocabastine eye drops (n = 32 patients) during a 14-day treatment period involving 113 children (aged 4 to 12 years) suffering from seasonal allergic conjunctivitis/rhinoconjunctivitis. The primary variable was the response rate defined as the number of patients showing an improvement after three days of treatment of at least three score points, from a minimum baseline score of six, in the main ocular symptoms of itching, conjunctival redness and lacrimation (each assessed on a four-point scale). Patients discontinuing due to inefficacy were regarded as non-responders. The mean response rate in the azelastine eye drops group (74%) was significantly higher (p < 0.01) than that in the placebo group (39%) and comparable with that in the levocabastine group. The response rates assessed by the patients in their diaries were very similar. Significant differences (p < 0.01) for azelastine compared with placebo were observed on days 3 and 14 in the mean sum scores for the three main symptoms and for a total of eight eye symptoms. The overall assessment of efficacy confirmed the superiority of both active treatments compared with placebo. Adverse drug reactions were reported in 23% of placebo-, 35% of azelastine- and 38% of levocabastine-treated patients. These were mainly local irritant effects. Overall tolerability was assessed as very good or good in 80%, 84% and 91% of placebo-, azelastine- and levocabastine-treated patients, respectively. Azelastine eye drops are effective and well-tolerated in children with seasonal allergic conjunctivitis.

Topics: Child; Child, Preschool; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Phthalazines; Piperidines; Rhinitis, Allergic, Seasonal; Severity of Illness Index

This study evaluated the effectiviness and the onset of action of levocabastine (CAS 79547-78-7) nasal spray and eyedrops as well as of nedocromil (CAS 69049-74-7) nasal spray and eyedrops in practical relevant circumstances. The study was designed as an open observational study with parallel groups in 10 centres and comprised 102 patients. All patients presented with seasonal allergic rhinitis and evidenced conjunctival symptoms requiring therapy. The patients as well as the investigators were required to rate the symptoms using symptom scores in order to evaluate the effectiveness of the used drugs. The effectiveness according to symptom scores did not differ significantly between investigator's and patient's judgment. Onset of action was within the first hour in 81.6% of the patients treated with levocabastine and in 82.9% of the patients treated with nedocromil. Symptoms were evaluated on a visual analogue scale ranging from 0 to 100. The use of both substances reduced the severity of the reported symptoms by 50% within the first hour. Thus, no significant difference in the onset of action could be observed even though a later onset of action was expected of the stabiliser of mast cell membranes. Both drugs were tolerated well.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Anti-Allergic Agents; Child; Child, Preschool; Conjunctivitis, Allergic; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nedocromil; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal; Time Factors

Levocabastine is an antihistaminic agent for topical application. It is without not advisable general side-effects and since many years is widely used for the treatment of pollinosis in adults and children more than 12 years of age. The group of 32 children aged from 5 to 11 years suffering from seasonal allergic rhinitis and conjunctivitis were treated by means of levocabastine applied topically by 20 days during the period of natural exposition to grass pollen. The clinical efficacy and tolerability including potential side-effects, were evaluated on the basis of clinical-laryngological investigations, visual analogs scales and diary cards filed in by parents of examined children. Levocabastine has been demonstrated to have rapid onset of action in children with SAR and the topical application of the drug does not irritate the mucosa of conjunctivas and nasal cavities.

Topics: Child; Child, Preschool; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal

Second-generation histamine H1-receptor antagonists are accepted first-line systemic therapy for seasonal allergic rhinitis. Ebastine is a new histamine H1-receptor blocker that may differ in efficacy from currently used second-generation agents.. To compare the efficacy of daily treatment with ebastine, 10 mg, ebastine, 20 mg, or cetirizine, 10 mg, for relieving symptoms of seasonal allergic rhinitis in adults.. In this multicenter, double-blind study, outpatients were randomized to one of three parallel treatment groups: ebastine, 10 mg, ebastine, 20 mg, or cetirizine, 10 mg once daily in the morning for a 2-week period. Patients were evaluated clinically according to symptoms, discomfort, and a global assessment at baseline and on days 8 and 15 of treatment. The total symptom score, defined as the sum of the total morning score on the day of evaluation and the total evening score on the preceding day, was the primary efficacy parameter.. Ebastine, 20 mg (n = 111), ebastine, 10 mg (116), and cetirizine, 10 mg (116), were all effective for improving nasal and ocular symptoms. There was, however, a general trend towards more rapid relief of symptoms with ebastine, 20 mg, and this reached statistical significance in some efficacy parameters after the first week of treatment. In a subpopulation of 158 patients who presented with more severe symptoms, statistically significantly greater improvement was seen with ebastine, 20 mg, compared with ebastine, 10 mg, as indicated by the mean change from baseline in the total symptom score averaged over the treatment period (-13.7 +/- 4.7 vs -11.8 +/- 3.8; P =.027) and in the morning symptom score (-6.7 +/- 2.7 vs -5.7 +/- 2.2; P = .042). All three treatments were well tolerated. Dry mouth, headache, and somnolence were the most common adverse events.. Ebastine (10 mg), cetirizine (10 mg), and ebastine (20 mg) administered orally once daily for 2 weeks all appear to be effective for relieving the symptoms of seasonal allergic rhinitis. Ebastine, 20 mg, may have advantages over ebastine, 10 mg, and cetirizine, 10 mg, in terms of a reduced time to achieve maximal efficacy and a superior level of efficacy in patients with more severe symptoms.

Topics: Adult; Butyrophenones; Cetirizine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Seasonal

396 adult and adolescent patients with seasonal allergic rhinitis participated in this randomised double-blind parallel-group study in which the efficacy and tolerability of ebastine 10 or 20mg administered once daily in the morning or evening for 3 weeks were compared with those of placebo. Clinical efficacy was assessed by measuring improvement in rhinitis symptoms (nasal discharge, nasal stuffiness, sneezing, itchy nose and itchy/watery eyes) recorded by patients twice daily on diary cards. The improvement in individual and total symptom scores at the end of the 3-week treatment period in patients treated with ebastine 10mg in the morning or ebastine 20mg in the morning or evening was significantly greater than the improvement in placebo recipients. The 20mg dose of ebastine administered in the morning was associated with the greatest improvement in symptom scores. There was no significant effect with the 10mg evening dose compared with placebo. Ebastine was well tolerated by the majority of patients - the incidence of adverse events, including headache, dry mouth, somnolence and asthenia being similar to that reported in placebo recipients. Electrocardiograms showed no evidence of any clinically relevant changes in QTc intervals. In a subsequent nonblinded 4-month study that included 230 patients from the initial study, global evaluations at monthly intervals showed overall symptom improvement in > or = 72% of patients who received ebastine 10mg or 20mg once daily. The drug was well tolerated during prolonged therapy, with adverse events being similar in nature and incidence to those reported in the 3-week double-blind study. In conclusion, ebastine 10mg once daily in the morning is an appropriate starting dose for the treatment of rhinitis, and this can be increased to 20mg as required.

Topics: Adolescent; Adult; Butyrophenones; Child; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; United States

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Butyrophenones; Cetirizine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

The efficacy of the second generation antihistamine ebastine has been investigated in the treatment and prevention of seasonal allergic rhinitis (SAR). In a double-blind randomised study, patients treated with a single daily dose of ebastine 10mg (n = 116) for 2 weeks showed a significant improvement in symptoms of SAR compared with those treated with placebo (n = 85). Sneezing, rhinorrhoea, tears and conjunctival irritation were all significantly improved, but not blocked nose. The overall efficacy of treatment was judged to be significantly superior in the ebastine group. There was no increase in bodyweight at the end of the study in either of the groups. There was no increase bodyweight at the end of the study in either of the groups. The percentage of patients reporting adverse events were headache, somnolence, nausea, dry mouth, stomach upset and increased appetite. The efficacy of ebastine 10 mg/day (n = 111) was similar to that of astemizole 10 mg/day (n = 106) over a 4-month period in preventing the symptoms of SAR in the open randomised study. The efficacy of both drugs in preventing the onset of sneezing, rhinorrhoea, blocked nose and tears was significant, when symptoms were compared with those during the previous year. At the end of the study, the astemizole-treated patients had a significant increase in bodyweight, which was not observed in the ebastine group. The percentage of patients reporting adverse events was significantly greater in the astemizole group (34.9% versus 20.7%; p = 0.02). Thus, ebastine is a useful alternative treatment for seasonal allergic rhinitis. It has also shown efficacy comparable to that of astemizole in the prevention of onset of symptoms of this allergic condition, and appears to be better tolerated than this agent.

Topics: Astemizole; Butyrophenones; Double-Blind Method; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Seasons

A total of 22 asymptomatic patients with a documented history of allergic rhinitis participated in this single-centre, double-blind, randomized, placebo-controlled, cross-over trial undertaken to assess the efficacy and tolerability of levocabastine nasal spray (0.5 mg/ml) in the prevention of allergen-induced nasal symptoms. Objective assessment of nasal symptoms revealed that the severity of sneezing was significantly lower following treatment with levocabastine (p < 0.001), with rhinorrhoea also tending to be less severe in the levocabastine-treated group (0.05 < p < 0.1). Rhinomanometry and acoustic rhinometry failed to reveal any significant intergroup differences, and there were no differences in nasal albumin concentrations between the two treatment groups. Patients' VAS ratings revealed significant differences in favour of levocabastine for sneezing (p < 0.001) and itching (p < 0.05), with the severity of rhinorrhoea also tending to be lower during treatment with this topical antihistamine (0.05 < p < 0.1). The mean total symptom score was also significantly lower in levocabastine-treated patients (p < 0.05). Levocabastine was well tolerated. Only two adverse events were reported: fatigue in one patient, and vesicular rash with facial oedema and urticaria in another. In conclusion, intranasal levocabastine provided effective protection from nasal allergen challenge and would appear to be a valuable therapeutic approach in patients with allergic rhinitis.

Topics: Administration, Intranasal; Adult; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Seasonal; Severity of Illness Index

Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 mumol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.

Topics: Adolescent; Adult; Allergens; Butyrophenones; Cross-Over Studies; Double-Blind Method; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine H1 Antagonists; Humans; Leukotriene C4; Male; Middle Aged; Nasal Polyps; Piperidines; Pollen; Prostaglandin D2; Rhinitis, Allergic, Seasonal

In this international, multicentre, randomized, double-blind, parallel-group, placebo-controlled trial 262 patients participated to assess the efficacy and tolerability of levocabastine nasal spray in the treatment of seasonal allergic rhinitis. Patients were randomized to receive either twice daily 0.05% levocabastine or matching placebo nasal spray with a treatment duration of four weeks. Assessments of global therapeutic efficacy favoured levocabastine. At the end of the trial, 55% of levocabastine-treated patients considered therapeutic efficacy to be excellent or good compared to 36% of those who received placebo (p < 0.001). The corresponding values for the investigator assessments were 54% and 37% (p < 0.001), respectively. Analysis of patients' diary data showed significantly lower AUCs for all parameters in the levocabastine group (p < 0.05). Investigator assessments revealed a trend towards a greater reduction in individual symptom severity from baseline in levocabastine-treated patients compared to placebo-treated controls. Adverse experiences were reported by 21% of levocabastine-treated patients and by 19% of those who received placebo, with no statistically significant differences in incidence or type. Headache and local reactions following application were the most frequently reported adverse events. Levocabastine nasal spray appears to be effective and well-tolerated for the treatment of seasonal allergic rhinitis and is an alternative to oral antihistamines.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

The efficacy and safety of the nasally administered histamine H1 receptor blocking drug azelastine was investigated in a randomized comparative trial with ebastine. Patients were treated for 14 days and efficacy was assessed by the physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was measured on the basis of reported adverse events. Data from a total of 59 patients were included in the efficacy analysis. Both treatment groups had dramatic reductions in the physician's total symptom score following treatment. Mean scores in the azelastine group decreased from 12.4 pretreatment to 5.6, while the mean ebastine scores decreased from 13.6 to 6.6. There was no significant difference between the two groups (p = 0.86). Changes in individual rhinitis symptoms showed no differences between the two groups. The majority of patients in both treatment groups reported an initial relief of symptoms within 1 h of dosing. For seven patients treated with azelastine, the initial effect was already seen after 10 min (ebastine: two patients). Eight adverse events were reported in each treatment group; all were mild except one report of sedation in an ebastine patient, which was of moderate severity. Three patients reported somnolence during treatment with ebastine. A bitter taste was mentioned by four patients in the azelastine group, but neither somnolence nor sedation was reported with azelastine. In conclusion, the results of the study suggest that both azelastine and ebastine are effective treatments of the symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Butyrophenones; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Phthalazines; Piperidines; Rhinitis, Allergic, Seasonal; Treatment Outcome

This multicenter, double-blind, double-dummy, parallel-group trial was initiated to compare the efficacy and tolerability of two antihistamines, topical levocabastine (eye-drops and nasal spray) and oral loratadine, for the treatment of seasonal allergic rhinoconjunctivitis in the primary care setting. A total of 95 adult patients participated in the study with a treatment duration of 5 weeks. Forty-seven patients were randomized to receive twice daily levocabastine eye-drops and nasal spray plus an oral placebo, and 48 to receive once daily oral loratadine with placebo eye-drops and nasal spray. Naphazoline eye-drops and xylometazoline nasal spray were permitted as rescue medication. No statistically significant intergroup differences in therapeutic efficacy were observed. Symptom severity was comparable in the two treatment groups throughout the trial period. At the end of the study, 86% of levocabastine-treated patients considered global therapeutic efficacy to be excellent or good, as compared with 77% of those who received loratadine. This difference was not statistically significant. There were no significant differences in the use of rescue medication or in the incidence or severity of adverse events in the two treatment groups. In conclusion, levocabastine eye-drops and nasal spray appear to be as effective and well tolerated as oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adult; Aerosols; Aged; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal

Children (n = 110) with seasonal allergic rhinoconjunctivitis were randomized to receive either twice daily 0.05% levocabastine eye drops and nasal spray plus twice daily topical placebos or 2% sodium cromoglycate eye drops and nasal spray four times daily for a period of 4 weeks. Patients were required to use the nasal sprays as directed and the eye drops only when required. The results obtained suggest that topical levocabastine is at least as effective as sodium cromoglycate for the treatment of this condition. After 2 weeks treatment the effect of therapy on nasal symptoms was considered to be excellent or good in 72% of levocabastine-treated patients and 54% of patients on sodium cromoglycate (p = 0.009), with corresponding values for ocular symptoms of 81% and 57% in the two groups, respectively (p < 0.05). Investigator assessments also revealed that the severity of sneezing and lacrimation were significantly lower in the levocabastine group at this time (p < 0.05). After 4 weeks of treatment, patient diary data revealed that levocabastine was at least as effective as sodium cromoglycate with intergroup differences attaining statistical significance in favor of the topical antihistamine for nasal congestion (p < 0.05). Both agents were well-tolerated with no significant differences in the incidence or type of adverse reactions in the two treatment groups.

Topics: Administration, Intranasal; Adolescent; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Administration, Topical; Adult; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Seasonal

This double-blind, parallel-group study compared topical levocabastine (eye drops and nasal spray) and oral terfenadine in 27 patients with seasonal allergic rhinoconjunctivitis over a period of 8 weeks. The main aim of this trial was to assess the ocular tolerability of levocabastine eye drops. Comparison of therapeutic efficacy was a secondary study objective. Use of oral and ocular medication was mandatory, however the nasal spray was only to be used when required. The use of nasal spray was 46% in the levocabastine group and 56% in the terfenadine group. Ophthalmologic examinations indicated that levocabastine eye drops were well tolerated. The incidence of adverse reactions was 31% in the levocabastine group and 43% in the terfenadine group. At the end of the trial, a total of 88% of levocabastine-treated patients rated the effect of therapy on ocular symptoms to be excellent or good compared with 75% of those who received terfenadine, while 75% of patients in each group were satisfied with the effect of therapy on nasal symptoms. The investigator's evaluation of symptom severity revealed consistently better results with levocabastine. Levocabastine was significantly more effective than terfenadine in relieving ocular itching (p = .02). The patients' visual analogue scale ratings also showed significantly better results for levocabastine, particularly with respect to nasal symptoms. Levocabastine was significantly better than terfenadine for a number of symptoms on days when the pollen count was high. In conclusion, topical levocabastine appears to be a well-tolerated and effective alternative to oral terfenadine for the treatment of seasonal allergic rhinoconjunctivitis.

Topics: Administration, Oral; Administration, Topical; Adult; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

This study was undertaken to compare the efficacy of twice-daily levocabastine, a new topical H1-blocking antihistamine, with that of twice-daily oral terfenadine in the treatment of allergic rhinoconjunctivitis. A total of 128 adult patients with a history of birch-pollen-provoked allergic rhinoconjunctivitis participated in this double-blind, parallel-group study. Ocular and nasal symptoms, assessed by a 100-mm visual analog scale, were recorded daily on diary cards for a period of 8 weeks. Global assessments of treatment efficacy were also performed. Conventional statistical analysis detected no significant differences between the two treatment regimens. Similarly, there was no difference in the number or type of adverse reactions in each treatment group. Statistical analysis according to Hauck & Anderson confirmed equivalence between the two treatment regimens. Topical levocabastine appears to be as effective and well-tolerated as oral terfenadine in the treatment of allergic rhinoconjunctivitis.

Topics: Administration, Intranasal; Administration, Oral; Adult; Conjunctivitis, Allergic; Double-Blind Method; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

This study was designed to compare the efficacy and tolerability of a new topical (nasal spray and eye drops) H1-receptor antagonist, levocabastine, with that of orally administered terfenadine for the prophylaxis and treatment of seasonal allergic rhinoconjunctivitis.. A total of 115 patients with documented birch pollen allergy were enrolled in this randomized, double-blind, double-dummy, parallel-group trial. Treatment was initiated immediately before the birch pollen season started and continued for a total of 8 weeks. Xylometrazoline (Otrivin) nasal spray was permitted as rescue medication.. The investigator's evaluation of symptoms showed similar effects for levocabastine and terfenadine. Both the patients' and the investigator's global evaluations of ocular and nasal symptoms disclosed a somewhat higher percentage of good or excellent results for levocabastine, but the differences were not statistically significant. Visual analog scale ratings from the patients' diaries showed better results for levocabastine. Levocabastine was significantly more effective than terfenadine in relieving sneezing, rhinorrhea, lacrimation, itch, and burning sensation (p < 0.05). For some symptoms, levocabastine was significantly more effective than terfenadine on days when the pollen count was high. There were no statistically significant differences in the use of rescue medication or in the incidence of adverse reactions reported in each treatment group.. In the present study topical levocabastine was frequently more effective than orally administered terfenadine for the treatment of seasonal allergic rhinoconjunctivitis. Both drugs were well-tolerated.

Topics: Administration, Oral; Adult; Aerosols; Conjunctivitis, Allergic; Double-Blind Method; Drug Tolerance; Female; Histamine H1 Antagonists; Humans; Male; Norway; Ophthalmic Solutions; Piperidines; Remission Induction; Rhinitis, Allergic, Seasonal; Terfenadine

The efficacy and safety of the nasal administration (twice in each nostril, four times a day) of levocabastine (0.5 mg/ml) were compared with those of sodium cromoglycate (20 mg/ml) and placebo in a 2-week, parallel, double-blind trial in patients with seasonal allergic rhinitis. At the end of treatment, 89% of patients in the levocabastine-treated group rated their treatment as globally good or excellent as compared with 32% (p = 0.003) of sodium cromoglycate-treated and 35% (p = 0.002) of placebo-treated patients. According to the investigators' ratings, the severest nasal symptom and ocular complaints responded better to levocabastine than to cromoglycate (p = 0.05 and p = 0.03) or placebo treatment (p = 0.03 and p = 0.001). Visual analogue scale ratings in patients' diaries indicated that at the end of therapy, nasal symptoms were less severe in the levocabastine-treated group than in the sodium cromoglycate-treated (p = 0.03) or placebo-treated group (p = 0.001). Total symptom severity as a percentage of the theoretical maximum symptom severity during the treatment period was lower for levocabastine than for sodium cromoglycate (p = 0.06) or placebo (p = 0.004) for the severest nasal symptom (35% versus 47% and 76%), sneezing (the most frequent symptom) (27% versus 42% and 67%), and itchy nose (18% versus 37% and 67%). The percentage of days at which nasal symptoms were entirely absent was markedly higher in the levocabastine-treated (33%) than in the sodium cromoglycate-treated (9%; p = 0.006) or placebo-treated (3%; p = 0.001) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Administration, Topical; Adolescent; Adult; Cromolyn Sodium; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Placebos; Rhinitis, Allergic, Seasonal

Nasal levocabastine (0.5 mg/mL) was evaluated for efficacy and tolerance against sodium cromoglycate (20 mg/mL) in a 2-week double-blind trial in 27 and 29 patients with seasonal allergic rhinitis. Globally at 2 weeks, the investigators found a 74% response rate in the levocabastine patients versus a 50% response rate in the cromoglycate patients (P less than .10). Sneezing responded better to levocabastine than to cromoglycate according to three efficacy indicators derived from patient diary ratings of symptom severity: sum of severity scores over the total treatment period as a percentage of the theoretical maximum sum of severity scores (median: 19% versus 41%, P = .01); percentage of symptom-free days (median: 46% versus 22%, P less than .07); percentage of days with moderate or severe symptoms (median: 0% versus 29%, P = .004). Further, the percentage of days with moderate or severe runny nose was lower than in cromoglycate patients (median: 0% versus 25%, P = .09). Although no significant differences were found for itchy nose, blocked nose, and ocular symptoms, severities tended to be generally less under levocabastine than under sodium cromoglycate. Adverse experiences were low level and of similar incidence in the two groups. It is concluded that in a q.i.d. schedule, levocabastine nasal spray is more efficacious than sodium cromoglycate in relieving sneezing and that it is equally well tolerated.

Topics: Administration, Intranasal; Adolescent; Adult; Child; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Severity of Illness Index

Fifteen asymptomatic subjects with allergic rhinitis participated in a double-blind, randomized, crossover, placebo-controlled study. The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash-out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen-induced reflex-mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.

Topics: Administration, Topical; Adult; Airway Resistance; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Male; Nasal Provocation Tests; Nose; Piperidines; Random Allocation; Ranitidine; Rhinitis, Allergic, Seasonal

Ebastine is an H1 antihistamine. Using a double-blind, parallel group randomized study design, the efficacy and the tolerability of oral ebastine (10 mg daily escalating to 40 mg daily according to clinical need) was compared over 4 weeks during 1986 with matching placebo in 40 general practice patients suffering from hayfever. Ebastine (19 patients) was more effective (P less than 0.05) than placebo (21 patients) against symptoms of running nose, itching nose, sneezing and blocked nose. Ebastine was superior to placebo in respect of the total symptom score as well as when judged by the investigators' and the patients' opinion of overall efficacy. Ebastine caused few adverse events, none of which resulted in a patient being withdrawn from treatment. Significantly more patients were withdrawn because of inefficacy from the placebo (n = 12) than from the ebastine (n = 3) treatment group (P less than 0.02). It is concluded that ebastine (10-40 mg daily) is an effective and well tolerated treatment for hayfever.

Topics: Adult; Butyrophenones; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Seasonal

Forty-four patients, with symptoms of nasal obstruction, sneezing, itching and/or rhinorrhea, were entered into a placebo-controlled, double-blind study to evaluate the clinical efficacy of a topical antihistamine drug, levocabastine, applied 4 times a day for 14 days. At the end of the treatment the placebo patients were treated with levocabastine and the levocabastine patients were treated with beclomethasone dipropionate in a single-blind design for another 14 days. This study showed that levocabastine is significantly more active than placebo with reference to nasal discharge and sneezing. Placebo application improved the symptom score. Levocabastine could not be proved to be more effective against nasal obstruction than placebo in the double-blind trial. In the single-blind set-up, levocabastine resulted in an additional improvement in the score for obstruction, after the placebo period. Although the allergic group tended to respond better, no statistically significant difference could be detected between allergic and non-allergic patients. After treatment with levocabastine, beclomethasone dipropionate administration could not improve the results for nasal discharge and sneezing. For nasal congestion, beclomethasone dipropionate proved to be superior to levocabastine.

Topics: Administration, Intranasal; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Levocabastine is a new selective H1 receptor antagonist. The effect of the drug administered locally was compared to placebo in a quantified nasal and conjunctival provocation test with allergens performed in patients allergic to grass pollen. In the nasal provocation test, levocabastine was able to increase the 'reaction threshold' (dose of allergen necessary to trigger allergic symptoms) in 9 out of 12 patients; the drug inhibited rhinorrhea and sneezing, but not nasal obstruction. In the conjunctival provocation test, the 'reaction threshold' clearly increased in 10 out of 11 patients. The local administration of levocabastine might be useful in allergic rhinitis and conjunctivitis.

Topics: Administration, Topical; Adolescent; Adult; Child; Conjunctivitis, Allergic; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Seasonal

Sixty-six patients with seasonal allergic rhinitis due to birch pollens, participated in an efficacy evaluation of topically applied, nasal and ocular, levocabastine, a highly selective H1 antagonist. A single blind comparison was performed between nasal levocabastine and flunisolide, a topical glucocorticoid preparation. Ocular levocabastine was compared with topical naphazoline/antazoline eye drops. Nasal and ocular symptom scores were recorded during a 31-day period. Pollen counts of birch pollens were done simultaneously. A global assessment of treatment efficacy was also made. In the comparison between the ocular treatments a significantly higher number of patients cited levocabastine excellent--it also had the advantage of fewer daily administrations. For nasal symptom scores the topical glucocorticosteroid therapy was in favour by number of sneezes. As for side effects, 44% of the patients complained of local irritation from naphazoline/antazoline eye drops or flunisolide nasal spray, but none with the levocabastine preparations. Topical levocabastine may provide an interesting alternative in the treatment of allergic rhinoconjunctivitis.

Topics: Administration, Intranasal; Adolescent; Adult; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Random Allocation; Rhinitis, Allergic, Seasonal

A double-blind study of terfenadine and placebo in 110 patients suffering from hay fever (confirmed by skin tests) was conducted. A novel technique was applied using an escape envelope containing a reference drug which could be taken under controlled conditions if, after 48 hours, the patient experienced no relief. Significantly more patients on placebo opened the envelope than patients taking the active drug. Terfenadine was demonstrated to be an effective drug in hay fever and produced no more drowsiness than placebo.

Topics: Adult; Benzhydryl Compounds; Chlorpheniramine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Placebos; Rhinitis, Allergic, Seasonal; Terfenadine

Topics: Administration, Oral; Adolescent; Adult; Aged; Aminopyrine; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Ascorbic Acid; Capsules; Child; Child, Preschool; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Decongestants; Nylidrin; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Rutin

Topics: Desensitization, Immunologic; Drug Evaluation; Histamine H1 Antagonists; Piperidines; Pollen; Rhinitis, Allergic, Seasonal; Thiophenes; Tissue Extracts

Nasal challenge tests were used to compare the protective effect of pre-treatment with HC 20-511 (Ketotifen), a new antiallergic compound, clemastine, DSCG and beclomethasone dipropionate in 14 patients with hay fever. HC 20-511 and clemastine were tested in a double-blind fashion and DSCG and beclomethasone openly. Most of the patients experienced an intense nasal reaction when challenged with pollens without pre-treatment. The intensity of nasal reactions was determined by subjective symptoms, clinical findings and nasal peak expiratory flow values. All the drugs tested relieved the symptoms and signs induced by pollens in nasal challenge tests. This tendency was not, however, statistically significant for any of the drugs. When using the changes in nasal expiratory flow rate as a criterion of protectiveness, the differences among the compounds tested were also slight. HC 20-511 seems to be a promising antiallergic agent. However, long term clinical trials still are needed to establish its efficacy in various allergic disorders.

Topics: Adolescent; Adult; Beclomethasone; Clemastine; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Female; Humans; Male; Peak Expiratory Flow Rate; Piperidines; Pollen; Pyrrolidines; Respiratory Function Tests; Rhinitis, Allergic, Seasonal; Thiophenes

In a double-blind study, diphenylpyraline (Lergobine) was given to 63 patients whose main symptoms were stuffiness of the nose, increased secretion of mucus, snuffling, sneezing and redness of the eyes. Fifty-seven patients were given placebo for identical symptoms. Diphenylpyraline was found to have a better effect on all the symptoms than placebo. The difference was statistically significant in respect of the discharge of mucus and redness of the eyes, and when the total symptoms were considered as a whole. In atopic patients the better effect of diphenylpyraline was highly significant.

Topics: Adolescent; Adult; Benzhydryl Compounds; Child; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Piperidines; Placebos; Rhinitis, Allergic, Seasonal; Skin Tests

Topics: Administration, Oral; Clinical Trials as Topic; Drug Evaluation; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Thiophenes

Topics: Adolescent; Adult; Aged; Chlorpheniramine; Clinical Trials as Topic; Drug Combinations; Ephedrine; Female; Humans; Male; Methods; Middle Aged; Nasal Decongestants; Phenylpropanolamine; Piperidines; Pulmonary Ventilation; Quaternary Ammonium Compounds; Rhinitis; Rhinitis, Allergic, Seasonal

Topics: Analysis of Variance; Clinical Trials as Topic; Diphenhydramine; Female; Histamine Release; Humans; Male; Piperidines; Promethazine; Rhinitis, Allergic, Seasonal; Skin Tests

These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen.. The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated.. Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period.. During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA.

Topics: Butyrophenones; Cryptomeria; Female; Histamine Antagonists; Humans; Interleukin-33; Interleukin-5; Interleukins; Male; Middle Aged; Nasal Mucosa; Piperidines; Pollen; Rhinitis, Allergic, Seasonal; Terfenadine

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

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 present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertussis toxin. Five days later, they were boosted by a subcutaneous injection of ovalbumin into the back. From day 18 after the first immunization to day 39, intranasal sensitization with ovalbumin was performed every day and the severity of allergic rhinitis was observed by measuring nasal allergic responses and total IgE levels. It was found that the intranasal administration of antigen caused a significant increase of nasal sneezing and rubbing from day 25 to day 39 both in sensitized HDC-KO and wild-type mice. In addition, a significant elevation of total IgE levels in serum was also found both in sensitized HDC-KO and wild-type mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose-dependent inhibition of nasal allergic responses induced by antigen in both HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose-related reduction of the nasal allergic responses induced by antigen in sensitized wild-type mice. On the other hand, they had no effects on the nasal signs induced by antigen in HDC-KO mice. From these results, it was revealed that substance P induces nasal allergic responses in the mouse model of chronic allergic rhinitis through the activation of tachykinin NK(1) receptors. Therefore, it can be concluded that not only histamine, but also substance P and prostaglandin D(2), participated in the nasal allergic responses induced by antigen in mice.

Topics: Animals; Behavior, Animal; Chlorpheniramine; Histamine H1 Antagonists; Histidine Decarboxylase; Hydantoins; Immunization; Immunoglobulin E; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurokinin-1 Receptor Antagonists; Ovalbumin; Piperidines; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic, Seasonal; Sneezing; Substance P

The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids during the pollinic period has been advised in this adolescent treated by betablockers.

Topics: Adolescent; Adrenergic beta-Antagonists; Anti-Asthmatic Agents; Butyrophenones; Cetirizine; Conjunctivitis, Allergic; Cromolyn Sodium; Diabetes Mellitus, Type 1; Heart; Histamine H1 Antagonists; Humans; Long QT Syndrome; Male; Piperazines; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

Topics: Anti-Allergic Agents; Butyrophenones; Cetirizine; Double-Blind Method; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Multicenter Studies as Topic; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Time Factors

Topics: Anti-Allergic Agents; Benzimidazoles; Butyrophenones; Cetirizine; Double-Blind Method; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Meta-Analysis as Topic; Piperidines; Placebos; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Butyrophenones; Electrocardiography; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Urticaria

Sepracor and Janssen are developing the histamine H1 antagonist, norastemizole (an active metabolite of Johnson & Johnson's Hismanal), for the potential, non-sedating treatment of allergy. Sepracor expects to file an NDA with the FDA by the fourth quarter of 2000 [337315,358429]. As of September 1999, Sepracor was conducting two large-scale phase III seasonal allergic rhinitis studies [340260]. Sepracor expects norastemizole to be the most potent non-sedating histamine, with equal or more rapid onset of action than other therapies [229516]. Norastemizole is 13- to 16-fold more potent as an H1 antagonist than astemizole and 20- to 40-fold more potent in inhibiting histamine-induced bronchoconstriction. Following a single dose of norastemizole (25 mg p.o.), there is significant attenuation of histamine-induced wheal and flare responses within 30 min. The drug's major advantage is its lack of cardiotoxicity or interactions with other drugs that increase the risk of developing serious arrhythmias [301469]. In July 2000, Morgan Stanley Dean Witter predicted filing for FDA approval for allergic rhinitis during the first half of 2001, and a partnership announcement around the time of this NDA filing. The analysts also forecast European sales of $8.3 million in 2002, rising to $16.7 m by 2005 [384868].

Topics: Animals; Anti-Allergic Agents; Benzimidazoles; Clinical Trials as Topic; Contraindications; Drugs, Investigational; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship

To test the efficiency and tolerance of the second generation antihistamine drug ebastin (kestine) in patients with seasonal allergic rhinitis (SAR).. Kestin was given for 3 weeks in doses 10 and 20 mg/day to 226 patients with SAR running for 6.8 +/- 6.1 years. SAR symptoms relief, subjective effects, side effects were studied.. The total index of rhinitis symptoms diminished from 11.6 to 1.2 scores. Subjective response was registered in 82% of the patients, objective in 77%. Neither treatment aggravations nor serious side effects occurred. 2 patients had drowsiness, head aches, dizziness and discontinued treatment.. Kestin is effective in SAR, had no serious side effects, is well tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Butyrophenones; Child; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Treatment Outcome

Topics: Adult; Butyrophenones; Cetirizine; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal

The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl] ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.

Topics: Animals; Antibodies, Monoclonal; Ascaris; Benzoates; Capillary Permeability; Carrageenan; Dermatitis, Contact; Edema; Female; Histamine Release; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; Passive Cutaneous Anaphylaxis; Piperidines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Adolescent; Asthma; Child; Child, Preschool; Female; Humans; Male; Piperidines; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal; Thiophenes

Topics: Acute Disease; Calcium; Chronic Disease; Humans; Laryngeal Edema; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Hyperthermia, Induced; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Anti-Allergic Agents; Antifungal Agents; Asthma; Conjunctivitis; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Central Nervous System Stimulants; Humans; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Tripelennamine

Topics: Central Nervous System Stimulants; Hyperthermia, Induced; Piperidines; Rhinitis, Allergic, Seasonal; Tripelennamine

Topics: Anti-Allergic Agents; Hyperthermia, Induced; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Tripelennamine; Urticaria

Topics: Humans; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Rhinitis, Vasomotor