piperidines and Conjunctivitis--Allergic

To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS).. The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use.. The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Cromolyn Sodium; Dibenzazepines; Histamine Antagonists; Humans; Hyperemia; Imidazoles; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Phthalazines; Piperidines; Pruritus; Pyridines; Pyrimidinones

Bepotastine besilate 1.5% is a newly approved second-generation topical antihistamine indicated for the pruritus associated with allergic conjunctivitis. In Japan, the oral formulation is approved to manage pruritus associated with allergic rhinitis and urticaria.. Bepotastine is a piperidine derivative that antagonizes H1 receptors with high selectivity. It has been labeled a dual-acting or multiple-acting antiallergic medication, because it inhibits histamine at H1 receptors and stabilizes mast cells to prevent histamine release. Bepotastine may also have other immunoactive properties, such as inhibition of eosinophil migration, interleukin-5 (IL-5), leukotrienes (e.g., LTB4) and platelet-activating factor (PAF). Human clinical trials demonstrate the efficacy and safety of systemic and ophthalmic bepotastine for pruritus relief, limited penetration across the blood-brain-barrier and kinetics suitable for twice-daily administration.. Bepotastine besilate 1.5% ophthalmic solution is a safe and effective treatment option for allergic conjunctivitis associated pruritus. Side-effect profile is similar to other ocular antihistamine agents. Additional comparative-effectiveness studies would further advance its clinical use. Oral bepotastine is a safe and effective treatment option approved in Japan for allergic rhinitis, urticaria and pruritus associated with skin diseases.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

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

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 purpose of this review is to examine published non-clinical literature on the antihistamine bepotastine besilate, including pharmacokinetic and pharmacologic properties.. Standard literature searches using diverse databases were used to find articles on bepotastine besilate published between 1997 and 2009. Articles primarily described non-clinical data utilized for the development of an oral formulation of bepotastine besilate and were published in Japanese. No publications of non-clinical data for an ophthalmic formulation were found in the database searches.. Bepotastine besilate is a second-generation antihistamine drug possessing selective histamine H(1) receptor antagonist activity. Bepotastine has negligible affinity for receptors associated with undesirable adverse effects, including histamine H(3), α(1)-, α(2)-, and β-adrenergic, serotonin (5-HT(2)), muscarinic, and benzodiazepine receptors. Bepotastine possesses additional anti-allergic activity including stabilization of mast cell function, inhibition of eosinophilic infiltration, inhibition of IL-5 production, and inhibition of LTB(4) and LTD(4) activity. Bepotastine in vivo dose-dependently inhibited the acceleration of histamine-induced vascular permeability and inhibited homologous passive cutaneous anaphylaxis in guinea pig studies. In mouse models of itching, oral bepotastine inhibited the frequency and duration of scratching behavior. Multiple in vivo animal toxicology studies have demonstrated bepotastine to be safe with no significant effects on respiratory, circulatory, central nervous, digestive, or urinary systems. The concentration of bepotastine after intravenous administration of bepotastine besilate (3 mg/kg) in rats was lower in the brain than in plasma, predicting reduced sedation effects compared to older antihistamines.. Non-clinical in vitro and in vivo studies have demonstrated bepotastine is a histamine H(1) receptor antagonist with favorable pharmacokinetic, pharmacologic, safety, and antihistamine properties as well as operating on other pathways leading to allergic inflammation beyond those directly involving the histamine H(1) receptor.

Topics: Animals; Anti-Allergic Agents; Conjunctivitis, Allergic; Disease Models, Animal; Drug Evaluation, Preclinical; Histamine Antagonists; Humans; Mice; Piperidines; Pruritus; Pyridines; Rats

The paper presents the main ocular injuries due to allergic mechanism and it point out the actual data about etiopathogenesis of type 1 hypersensitivity and immunologic mechanism involved in allergic keratoconjunctivitis. Then are exposed the classification of ocular allergy, the main signs and symptoms, the paraclinical methods of diagnosis and the actual agents of therapy.

Topics: Anti-Inflammatory Agents; Conjunctivitis, Allergic; Cyclosporine; Drug Therapy, Combination; Histamine H1 Antagonists; Humans; Immunoglobulin E; Immunosuppressive Agents; Ophthalmic Solutions; Piperidines; Prednisone

Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis was inhibited by levocabastine in several allergy models. Levocabastine moderately inhibited histamine-release from guinea pig conjunctive induced by antigen-antibody reactions and prevented an increase in the vascular permeability of the conjunctive elicited by both histamine and antigen instillation. Symptoms of allergic rhinitis, which were induced by histamine, substance P and antigen, were also reduced by levocabastine. Levocabastine prevented an increase in the vascular permeability of nasal mucosa elicited by instillation of these three inducers. Furthermore, levocabastine has shown a large difference between the antiallergic dose and other non-specific pharmacological effective dose than that with other antiallergic drugs. The non-specific pharmacological effect of levocabastine reveals only blepharoptosis. With these pharmacological effects and topical usage, levocabastine was shown to be useful for allergic conjunctive and rhinitis in both seasonal and perennial clinical use.

Topics: Animals; Chemotaxis, Leukocyte; Clinical Trials as Topic; Conjunctivitis, Allergic; Depression, Chemical; Disease Models, Animal; Eosinophils; Histamine H1 Antagonists; Histamine Release; Humans; Mast Cells; Neutrophils; Piperidines; Rhinitis, Allergic, Perennial

The article presents two topical antihistaminics: levocabastine and azelastine. Most attention is paid to discussing the pharmacokinetics and antihistamine, antiallergic and antiinflammatory activities of these drugs. Their clinical usefulness in allergic rhinitis and conjunctivitis is also presented. Finally the authors describe the adverse reaction observed after administrating of topical antihistaminics.

Topics: Administration, Topical; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Cytochrome P-450 Enzyme System; Histamine H1 Antagonists; Humans; Nasal Mucosa; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial

Allergic eye conditions, particularly seasonal allergic conjunctivitis (SAC), are common. Itching, oedema and hyperaemia are relieved with topical H1-antagonists or sodium cromoglycate. The newer mast-cell stabilizing agent nedocromil sodium has a similar safety profile to sodium cromoglycate, but is more potent and has a more convenient twice-daily dosing regimen. When several placebo-controlled studies of its use in the treatment of SAC were analysed, it was found that 80% of patients reported symptom relief. In a further study, nedocromil sodium eyedrops (twice-daily dosing) had similar overall efficacy to sodium cromoglycate eyedrops (four-times-daily dosing) in subjects with SAC during the birch season, but during the period of highest pollen challenge, only the former agent was significantly more effective than placebo. Another study found that nedocromil sodium had efficacy equivalent to levocabastine over 7 days, but tended to have a more rapid onset of action. In patients with perennial allergic conjunctivitis (PAC) unresponsive to sodium cromoglycate, both clinicians and patients reported significantly better control of symptoms with nedocromil sodium eyedrops than with placebo. Recently, in a long-term study of treatment for vernal keratoconjunctivitis (VKC), it was found that nedocromil sodium 2% eyedrops produced a more rapid and marked improvement in symptoms than sodium cromoglycate 2% eyedrops and enabled lower use of steroid rescue medication. Both drugs were well tolerated and without serious side-effects.

Topics: Anti-Allergic Agents; Conjunctivitis, Allergic; Controlled Clinical Trials as Topic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Nedocromil; Patient Satisfaction; Piperidines

Topical ocular allergy drugs are indicated for the treatment of allergic conjunctivitis after more conservative measures have been employed. Antihistamines, vasoconstrictors, nonsteroidal anti-inflammatory drugs, mast cell stabilizers and corticosteroids are available. Levocabastine and ketorolac tromethamine are new drugs for the treatment of allergic conjunctivitis. Lodoxamide is currently indicated only for the treatment of vernal keratoconjunctivitis, although treatment efficacy has been demonstrated in patients with giant papillary conjunctivitis and atopic keratoconjunctivitis. As a general rule, topical ocular allergy drugs are well tolerated by most patients except for transient stinging and burning on instillation. Ocular steroids should be reserved for severe cases and should be prescribed by an ophthalmologist, who can monitor the patient for possible ocular side effects.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ketorolac Tromethamine; Oxamic Acid; Piperidines; Tolmetin; Tromethamine

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

Levocabastine is a new topical histamine H1 antagonist. The antihistaminic and antiallergic effects of levocabastine eye drops have been evaluated in eight conjuctival provocation studies (n = 238). Two studies used a histamine challenge; five studies used allergen challenge; one study used both and in one study allergic provocation was with compound 48/80. In all but one study, only one single dose of levocabastine (one or two drops) was given. Six studies were against placebo only; one was against cromoglycate and one study used both placebo and cromoglycate as reference drugs. Single instillation of levocabastine eye drops protected against histamine and allergen-induced ocular symptoms within a period of 10 minutes. Levocabastine eye drops significantly alleviated conjunctival itching, redness, chemosis, eyelid swelling and tearing induced by histamine or allergen challenge (p < or = 0.05). Four hours after administration levocabastine was still active. With levocabastine, but not with cromoglycate, a significant increase was observed in the allergen threshold. Even when compared to cromoglycate given as a pre-treatment four times daily for two weeks before the allergen challenge, a single dose of levocabastine was significantly more effective in inhibiting hyperaemia, eyelid swelling, chemosis and tearing (all p < 0.05). In conclusion, conjunctival provocation studies have established that levocabastine has a rapid and long-lasting effect in protecting against histamine or allergen-induced conjunctival symptoms.

Topics: Conjunctivitis, Allergic; Evaluation Studies as Topic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Premedication

Histamine is the key mediator producing itching, redness and chemosis in allergic conjunctivitis. Histamine levels in tears are increased ten-fold in patients with this allergic condition. Levocabastine is a newly synthesized histamine H1 antagonist which has been formulated as both eye drops and nasal spray. In well established assays of antihistamine activity, levocabastine was found to be the most potent antihistamine compound available, being 15,000 times more potent than chlorpheniramine. Ocular provocation studies in man have shown that levocabastine protects against the symptoms of allergen-induced conjunctivitis. Ophthalmological examinations, including slit lamp and ophthalmoscopy showed no adverse effects. Data from therapeutic studies are available for more than 1700 patients with allergic conjunctivitis treated for 2-16 weeks. One drop of levocabastine (0.5 mg/ml) per eye given two to four times daily provided significantly better symptom control than placebo, with good to excellent results in 71% of patients on levocabastine compared to 55% on placebo (p < 0.001). Levocabastine has a fast onset of action. In one study 94% of patients experienced symptom relief within 15 minutes after the first instillation. The effects observed with levocabastine were at least as good as those with ocular cromoglycate or oral terfenadine. The incidence of adverse experiences was not different from placebo. Levocabastine promises to be a valuable treatment for patients with allergic conjunctivitis.

Topics: Animals; Antazoline; Conjunctivitis, Allergic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Naphazoline; Ophthalmic Solutions; Piperidines; Placebos; Terfenadine

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

Levocabastine is a long acting, highly potent and selective histamine H1-receptor antagonist, which has been developed for nasal and ocular administration. In controlled trials performed to date levocabastine was effective and well tolerated in the treatment of allergic rhinitis and allergic conjunctivitis. Comparative studies have demonstrated that levocabastine is superior to placebo and at least as effective as sodium cromoglycate (cromolyn sodium) in alleviating symptoms associated with seasonal allergic conditions. Although levocabastine appears to be less effective than the topical corticosteroid beclomethasone with regard to relieving runny and blocked nose, further comparative trials between these 2 agents would be desirable. Similar to other antihistamines, levocabastine provides minimal relief of nasal blockage, but this symptom is believed to be mediated by receptors other than histamine H1. The prompt onset of antiallergic activity after application differentiates levocabastine from the reference topical antiallergic, sodium cromoglycate, which has an onset of efficacy characterised by a lag period, thereby necessitating maintenance treatment. The incidence of adverse effects associated with levocabastine therapy is low and is similar to that observed with placebo and sodium cromoglycate. Levocabastine provides prophylactic protection as well as acute relief from nasal and ocular symptoms in patients with seasonal allergic disorders. With the ever increasing trend towards topical therapy for the treatment of allergic rhinitis and allergic conjunctivitis, levocabastine is a useful addition to the range of drugs currently available. Possible avenues for additional research should include determining whether the antiallergic efficacy of topical levocabastine is superior to that of oral agents such as astemizole and terfenadine, and whether topical therapy is indeed preferred, considering the relative ease of administration of effective oral antiallergic agents.

Topics: Administration, Topical; Animals; Conjunctivitis, Allergic; Cromolyn Sodium; Drug Evaluation; Drug Tolerance; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial

Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis.. Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated.. A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed.. All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Topics: Adult; Anti-Allergic Agents; Benzimidazoles; Conjunctivitis, Allergic; Double-Blind Method; Humans; Ophthalmic Solutions; Piperidines; Pruritus

To compare the efficacy and safety of Alcaftadine 0.25%, Olopatadine hydrochloride 0.2%, and Bepotastine besilate 1.5% ophthalmic solutions in the treatment of allergic conjunctivitis.. This is a prospective, observer-masked, comparative study of 180 patients with mild to moderate allergic conjunctivitis, randomized into three groups of 60 patients each. Each group was assigned to be treated with one of the three treatment options namely Alcaftadine 0.25%, Olopatadine hydrochloride 0.2% and Bepotastine besilate 1.5% ophthalmic solutions. Patients were followed-up at regular intervals with relief and resolution of symptoms and signs noted using Total Ocular Scoring System (TOSS) and hyperaemia scale.. All three topical medications were effective in resolving symptoms of the patients with mild to moderate allergic conjunctivitis. Baseline mean TOSS scores for Alcaftadine group, Olopatadine group and Bepotastine besilate group were (7.68±2.32), (7.65±2.32) and (7.45±2.27) respectively as compared to the corresponding TOSS scores on 14. All three topical ophthalmic medications used in the study are safe and effective in the treatment of allergic conjunctivitis. However, Bepotastine and Alcaftadine appear to outweigh Olopatadine in resolving the symptoms of allergic conjunctivitis.

Topics: Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Humans; Imidazoles; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Treatment Outcome

With increasing environmental pollution, the incidence of allergic conjunctivitis is increasing. Newer anti-allergic medications with combined anti-histaminic and mast cell stabilization action can help reducing the use of topical steroids for milder form of disease. There is no study directly comparing olopatadine (0.1%), bepotastine (1.5%), and alcaftadine (0.25%) for mild to moderate allergic conjunctivitis cases. Hence, we decided to methodically study the efficacy of three topical medications.. Prospective, observer-masked clinical trial enrolled 45 patients with 15 patients in each of the three groups. Patients with mild to moderate allergic conjunctivitis were sequentially assigned to respective groups, and relief of symptoms and signs were noted upto 1-month follow-up.. All three topical medications faired almost equally in resolving symptoms of the patients with mild to moderate allergic conjunctivitis, and most of them reported complete relief after 1 week of use of medication. Few cases with limbal or palpebral papillae reported symptomatic relief after use of medication, but the resolution of these signs was not noted in all three groups.. We concluded similar efficacy of three medications in relieving symptoms and inefficacy in regressing palpebral and limbal papillae in cases of allergic conjunctivitis.

Topics: Adolescent; Adult; Anti-Allergic Agents; Benzazepines; Child; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Imidazoles; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Single-Blind Method; Treatment Outcome; Young Adult

To evaluate the safety and efficacy of preservative-free levocabastine 0.05 % ophthalmic solution compared to placebo (vehicle) and to preserved levocabastine 0.05 % ophthalmic suspension in the prevention of allergic conjunctivitis induced by a conjunctival provocation test.. Ninety-two subjects (18-50 years) with a previous history of allergic conjunctivitis to pollen were randomised to receive either preservative-free levocabastine solution in one eye and preserved levocabastine suspension in the fellow eye (n=69), or preservative-free levocabastine in one eye and placebo in the fellow eye (n=23). One drop of each product was administered 10 minutes (visit 3) and 4 hours (visit 4) prior to the provocation test. The primary efficacy criterion was the sum of the itching and conjunctival hyperemia scores assessed at 3, 5 and 10 minutes after the provocation test. The safety evaluation included adverse events, visual acuity, intra-ocular pressure and study drug drop sensation.. The efficacy of the preservative-free solution was significantly higher than that of placebo at all time points (P≤0.01) with one exception at visit 4 (3 minutes after the provocation test). It was significantly higher than that of the preserved suspension at visit 3, and equivalent at visit 4. The incidence of adverse events was lower with the preservative-free solution than with the preserved suspension. 94.2 % and 95.7 % subjects rated preservative-free levocabastine drop sensation as "good" or "very good" at visits 3 and 4 respectively, whereas these rates were 68.1 % and 63.8 % with preserved levocabastine. This difference between the two formulations was highly statistically significant (P<0.001).. The efficacy of preservative-free levocabastine was superior to that of the placebo and of the preserved suspension at visit 3, at least as effective as the preserved suspension at visit 4, and better tolerated at each visit.

Topics: Administration, Ophthalmic; Adolescent; Adult; Allergens; Chemistry, Pharmaceutical; Conjunctiva; Conjunctivitis, Allergic; Diagnostic Techniques, Ophthalmological; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Preservatives, Pharmaceutical; Treatment Outcome; Young Adult

This clinical trial evaluated the safety and effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo for the treatment of ocular itching and conjunctival hyperemia (redness) using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis when dosed 16 h before a CAC test.. Subjects with a history of allergic conjunctivitis were assigned to receive placebo or bepotastine besilate ophthalmic solution 1.0% or 1.5% in a single-center, randomized, placebo-controlled clinical trial. Eligible subjects (n=107) aged 10 years and older with a history of allergic conjunctivitis who had a reproducible positive reaction to a CAC were enrolled and dosed with test agent. The primary trial objectives included assessment of ocular itching and conjunctival redness at 16 h after instillation of test agent. Reductions in several CAC-induced secondary symptoms and signs of allergic conjunctivitis were also evaluated for tearing, ciliary and episcleral redness, eyelid swelling, chemosis, and mucous discharge.. Bepotastine besilate ophthalmic solution 1.5% demonstrated clinical effectiveness and statistical significance in comparison to placebo for the reduction in CAC-induced ocular itching 16 h after drug administration. Bepotastine besilate ophthalmic solution 1.0% also achieved statistical significance in comparison to placebo for reducing ocular itching at all time points 16 h after dosing. Statistically significant reduction (P≤0.05) was additionally seen in this CAC test for the secondary ocular efficacy variable of allergen-induced tearing for bepotastine besilate ophthalmic solution 1.5%. No clinical benefit was seen for reducing the coprimary efficacy variable of conjunctival redness with the CAC model of allergic conjunctivitis.. Bepotastine besilate ophthalmic solution 1.5% produced predefined clinically meaningful reduction in CAC-induced ocular itching and tearing in a single-site trial and was more effective than bepotastine besilate ophthalmic solution 1.0% and placebo for reducing ocular itching in a CAC test 16 h after dosing.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Child; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperemia; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pruritus; Pyridines; Time Factors; Young Adult

To evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo at reducing ocular itching and conjunctival hyperemia in the conjunctival allergen challenge (CAC) model of allergic conjunctivitis.. Prospective, double-masked, randomized, placebo-controlled, phase 3 CAC clinical trial.. This multicenter trial enrolled 130 subjects with a clinical history of allergic conjunctivitis who were randomized to bepotastine besilate ophthalmic solution 1.0%, 1.5%, or 0.0% (placebo). One drop of test agent was instilled bilaterally before a CAC test evaluating responses at 15 minutes, 8 hours, or 16 hours after test agent instillation. Primary efficacy outcomes were unit improvements relative to placebo in mean scores for ocular itching and conjunctival hyperemia, each graded on 0- to 4-unit scales.. Reductions of 1.2 units or more in mean ocular itching scores at all time points for both bepotastine besilate ophthalmic solutions 1.0% and 1.5% were observed at onset of action and 8-hour duration-of-action CAC tests (P < .0001). Statistically significant reductions in conjunctival hyperemia (P < or = .0125) were observed for bepotastine besilate ophthalmic formulations only at the onset of action CAC test.. Bepotastine besilate ophthalmic solutions 1.0% and 1.5% both substantially decreased CAC-induced ocular itching for at least 8 hours after dosing. Reductions in conjunctival hyperemia after a CAC, although statistically significant for bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo when assessed at 15 minutes after dosing, were modest.

Topics: Adolescent; Adult; Anti-Allergic Agents; Child; Conjunctiva; Conjunctivitis, Allergic; Double-Blind Method; Female; Humans; Hyperemia; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Treatment Outcome; Visual Acuity

Bepotastine besilate is a selective histamine1-receptor antagonist and mast cell stabilizer with inhibitory effects on eosinophilic activity.. To evaluate the safety and efficacy of 1.5% bepotastine besilate ophthalmic solution in alleviating nonocular symptoms induced by a conjunctival allergen challenge (CAC), a clinical model of allergic conjunctivitis.. This was a single-center, double-masked, randomized, placebo-controlled clinical trial performed from March 1 to April 4, 2007. Patients 10 years or older with a history of allergic conjunctivitis and a reproducible, positive, clinical response to a CAC were eligible. Patients received either placebo or 1.5% bepotastine besilate, 1 drop in each eye. After 15 minutes, 8 hours, or 16 hours after dosing, a CAC was performed and patients evaluated nonocular symptoms using standardized grading scales.. Seventy-one patients were enrolled in the study, and 66 comprised the per protocol population. A clinically meaningful reduction (> or = 1.0 unit) compared to placebo was achieved for rhinorrhea and nasal congestion at most time points after 1.5% bepotastine besilate instillation at 8 hours before a CAC test. Significant reductions (P < or = .05) in mean values were seen with 1.5% bepotastine besilate at 15 minutes and 8 hours after dosing for CAC-induced nasal congestion, rhinorrhea, ear or palate pruritus, nasal pruritus, and summed nonocular composite symptom (NOCS) scores and also at 16 hours after dosing for nasal congestion and rhinorrhea.. The 1.5% bepotastine besilate formulation produced statistically significant reductions after a CAC in individual nonocular symptoms and NOCS scores at onset of allergic response and for at least 8 hours after instillation, with the greatest reduction seen for nasal congestion and rhinorrhea.

Topics: Adult; Allergens; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine Antagonists; Humans; Immunization; Male; Middle Aged; Nasal Obstruction; Ophthalmic Solutions; Piperidines; Pyridines

Bepotastine besilate is a highly selective histamine H(1)-receptor antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory activity. Based on a history of clinical effectiveness and tolerability of oral bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate is being tested as a potential ophthalmic medication for allergic conjunctivitis.. The aim of this study was to assess the effects of bepotastine besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in adults and children.. This Phase III, single-center, prospective, randomized, double-masked, placebo-controlled, CAC clinical trial enrolled patients >or=10 years of age with a history of allergic conjunctivitis, skin-test reaction, and CAC response. Patients received bepotastine besilate ophthalmic solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, 1 drop on each eye on days 14 +/- 3 and 28 +/- 3. The primary efficacy end points, patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator-assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical significance was defined in the protocol as >or=1.0-U between-group difference in mean ocular itching scores at the majority of time points at a study visit and also a >or=0.5-U difference at all time points. Tolerability of the test agent was assessed by visual acuity, slit-lamp biomicroscopy, intraocular pressure, dilated funduscopy, and adverse events.. A total of 107 patients (male, 54%; age range, 11-73 years; white race/ethnicity, 93%) received investigational product and comprised the intent-to-treat (ITT) population (bepotastine besilate ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution 1.5%, 35; and placebo, 36). All 107 patients received investigational product at visit 3A (day 0) and were included in the ITT population. Of the 107 patients who were enrolled, 103 completed the study without a protocol deviation or violation. The 1.0% and 1.5% solutions were associated with clinically and statistically significant reductions in mean ocular itching scores compared with placebo on the 15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions, 1.3-1.5 U and 1.0-1.7 U respectively; all, P < 0.001). Statistically significant reductions in conjunctival hyperemia were achieved with both bepotastine besilate concentrations. Overall, 13 patients experienced a treatment-emergent adverse event considered related to the study drug (bepotastine besilate ophthalmic solution 1.0%, 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and placebo, 3).. In this CAC model of allergic conjunctivitis in adults and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were associated with clinically and statistically significant reductions in ocular itching, but not conjunctival hyperemia, within 15 minutes that were maintained for at least 8 hours after administration. Both solutions were well tolerated. ClinicalTrials.gov identifier: NCT00424398.

Topics: Administration, Topical; Adolescent; Adult; Aged; Allergens; Anti-Allergic Agents; Child; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pruritus; Pyridines; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Allergic conjunctivitis is the most common form of conjunctivitis encountered in daily ophthalmological practice. Its therapy can be problematic: it must be simple, free of complications, and adaptable to everyday life.. We conducted a randomized prospective single-center survey on 102 patients between 4 and 80 years of age who presented moderate allergic conjunctivitis. Patients were divided into two groups, one treated in monotherapy with N-acetyl-aspartyl glutamic acid (NAAGA) over 4 weeks and the other treated with bi-therapy (NAAGA and Levocabastine during the first week and NAAGA only for the next 3 weeks), with evaluation of the sum of the scores of the cardinal signs of allergic conjunctivitis at D0, D7 and D28.. The two populations were homogeneous at inclusion: the majority of the patients had a history of allergies, with a nonspecific disrupted allergy workup (IgE and eosinophils) and a higher initial score for the children included in the study. The scores decreased sharply at D7 (50% reduction) and at D28 (bordering 1) with no significant difference between the two groups. Tolerance to the treatment judged by unusual sensations upon instillation was better for the NAAGA treatment (80.8% of the cases). Clinical and functional signs disappeared without recourse to corticoids.. In the moderate forms of seasonal and intra-annual allergic conjunctivitis, NAAGA treatment alone is sufficient. The association with Levocabastine is necessary only in cases of highly bothersome functional signs. The use of corticoids should be reserved for the serious forms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Child; Child, Preschool; Clinical Protocols; Conjunctivitis, Allergic; Dipeptides; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Seasons; Young Adult

To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone.. Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated.. The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings.. Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis, Allergic; Drug Therapy, Combination; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukocyte Count; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Pyridines; Pyrimidinones; Treatment Outcome

This comparative and randomised pilot study assessed the clinical and biological efficacy of Naaxia Sine(R) eye-drops versus levocabastine eye-drops in the treatment of vernal keratoconjunctivitis (VKC).. Twenty-three VKC patients were randomised and treated bilaterally for 28 days with N-acetyl-aspartyl-glutamate (NAAGA) or levocabastine (LEVO) eye-drops. The primary efficacy variable, overall evolution of eosinophil cationic protein (ECP) tear concentrations, was assessed in a masked fashion on D0, D7 and D28. Clinical symptoms and signs were reported at the same time points. Biological parameters were analysed with a non-parametric rank-based approach. Global tolerance was assessed by the investigator and patient.. At all time points, ECP tear levels were significantly reduced in the NAAGA compared with the LEVO group (p = 0.023). Reduction of eosinophil leucocytes and tear lymphocytes was higher not significant in the NAAGA group. The same trend was observed for the evolution of total ocular symptom score. There were no significant differences between treatment groups in the occurrence of adverse effects, except for burning which was more frequent in the LEVO group (p = 0.002).. The anti-eosinophilic actions of NAAGA were shown by a significant reduction of ECP tear concentrations. A decreased lymphocyte count and an overall improvement of the symptomatology were also noted. Moreover, the tolerability of NAAGA appeared to be better.

Topics: Anti-Inflammatory Agents; Child; Conjunctivitis, Allergic; Dipeptides; Eosinophil Cationic Protein; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Lymphocyte Count; Male; Ophthalmic Solutions; Osmolar Concentration; Pilot Projects; Piperidines; Preservatives, Pharmaceutical; Tears; Treatment Outcome

This study was conducted to investigate the efficacy and safety of 0.025% levocabastine hydrochloride in Japanese subjects with seasonal allergic conjunctivitis and its duration of action using the conjunctival allergen challenge (CAC) test.. Twenty-four asymptomatic subjects were randomized to instill 0.025% levocabastine ophthalmic suspension in one eye and vehicle in the other eye 10 minutes before the CAC test. Signs and symptoms of allergic conjunctivitis were scored 10, 15, and 25 minutes after the CAC test. The duration of drug effects was also evaluated by allergen rechallenge 4 hours after levocabastine administration. The itching score for each eye as the primary efficacy endpoint was assessed 15 minutes after the CAC test using a 5-point scale.. The mean itching score in the levocabastine-treated group was 0.08 +/- 0.06, which was significantly lower than the mean score of 1.98 +/- 0.16 in the vehicle group (P < 0.0001). The redness and chemosis of the conjunctiva were also improved significantly compared with the vehicle group. Levocabastine showed prolonged efficacy in inhibiting itching (0.42 +/- 0.12 vs 0.94 +/- 0.17, P < 0.0002) and redness (1.04 +/- 0.18 vs 1.42 +/- 0.22, P < 0.01) of the conjunctiva upon the rechallenge test. No significant topical or systemic adverse safety findings were observed in the levocabastine group.. The results indicate that 0.025% levocabastine ophthalmic suspension is effective and safe in the treatment of allergic conjunctivitis with a duration of action of at least 4 h.

Topics: Adult; Allergens; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Japan; Male; Ophthalmic Solutions; Piperidines; Seasons; Suspensions; 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

In order to assess the efficacy of an antihistaminic eye drop containing 0.05% mequitazine in the prevention of allergy induced by a conjunctival provocation test, a double-masked, randomized, intraindividual study compared this eye drop to 0.05% levocabastine and 0.1% dexamethasone eye drops in 24 subjects allergic to grass pollen.. During the first phase of treatment, randomized subjects received one drop of dexamethasone in one eye and one drop of either mequitazine or levocabastine in the fellow eye. During the second phase of treatment, they were given one drop of dexamethasone in the same eye as previously, and one drop of the treatment that had not been given during the first phase (levocabastine or mequitazine) in the fellow eye. Fifteen minutes after each instillation phase, a conjunctival provocation test was performed. Hyperemia, itching, tearing, chemosis and palpebral edema were the five signs or symptoms taken into account to assess the treatment efficacy. Their intensity was evaluated 3, 5 and 10 min after the conjunctival provocation test. The primary efficacy criterion was the global score obtained by measuring hyperemia and itching intensity.. The score was reduced significantly more (p < 0.0001) for the eyes treated with mequitazine or levocabastine than for those treated with dexamethasone at all evaluation times. The difference was also significant for hyperemia (p < 0.001), itching (p < 0.001), and tearing (p < 0.05). The tolerability of the three eyedrops was satisfactory.. Mequitazine and levocabastine were safe and significantly more effective than dexamethasone in preventing the allergic response induced by a conjunctival provocation test when they were instilled 15 min before contact with the allergen.

Topics: Adult; Allergens; Anti-Allergic Agents; Anti-Inflammatory Agents; Conjunctiva; Conjunctivitis, Allergic; Data Interpretation, Statistical; Dexamethasone; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Phenothiazines; Piperidines; Time Factors

A double masked randomised trial comparing 0.05% mequitazine eye drops with 0.05% levocabastine and placebo was carried out in otherwise healthy volunteers allergic to house dust mites (Dermatophagoides pteronyssinus).. Double masked, randomised, single centre study, comparing three parallel treatment groups. 60 healthy adults with a confirmed history of allergic conjunctivitis to house dust mites for at least 2 years were included and completed the trial. Conjunctival provocation tests (CPT) were done at screening, at visit 2 (V2) (1 week later), and at visit 3 (V3) (2 weeks after V2). Treatment was instilled in the same eye, 5 minutes after the CPT at V2, and twice daily until V3. CPT were scored 5, 10, 15, and 60 minutes after instillation of the dose of Dermatophagoides pteronyssinus antigen determined at inclusion (V2, curative test) or resulting in positivity (V3, preventive test). In the V2 (curative) test the difference between the active treatments and placebo on the redness+itching scores was not significant. At the V3 (preventive) CPT there was a lower number of reactions at the threshold dose with mequitazine (20%) compared to placebo (60%, p = 0.01) or levocabastine (45%, p = 0.10).. This trial failed to clearly demonstrate curative superiority of topical antihistamines with placebo, when a single dose of treatment was instilled following CPT. However mequitazine 0.05% eye drops were superior to placebo in preventing a reaction to CPT, after 2 weeks of treatment.

Topics: Adolescent; Adult; Chi-Square Distribution; Conjunctivitis, Allergic; Dermatophagoides pteronyssinus; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Phenothiazines; Piperidines; Statistics, Nonparametric

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

To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.. The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0-4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27 min after topical drug administration, such that the first post-challenge assessment was made 30 min post-drug instillation. Allergic signs and symptoms were evaluated at 3 min, 10 min, and 20 min postchallenge and safety and efficacy analyses were performed.. Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3 min and 10 min post-challenge (p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.. Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.

Topics: Adolescent; Adult; Aged; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Severity of Illness Index; Treatment Outcome

Azelastine is a selective H(1)-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC). The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo.. A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment.. Azelastine significantly improved itching and conjunctival redness compared to placebo (p < 0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9 +/- 1.1 and with levocabastine by 1.5 +/- 1.2 compared to placebo (0.6 +/- 1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction.. Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analysis of Variance; Anti-Allergic Agents; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial

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

Ketotifen blocks histamine H(1) receptors, stabilises mast cells, and prevents eosinophil accumulation. These multiple, pharmacological mechanisms provided the rationale for assessing the efficacy and safety of ketotifen 0.025% eye drops in subjects with seasonal allergic conjunctivitis (SAC) in an environmental setting.. This was a double masked, randomised, multicentre trial conducted in Australia. Subjects were randomly assigned to ketotifen fumarate 0.025% ophthalmic solution, placebo (as vehicle), or levocabastine hydrochloride 0.05% ophthalmic suspension, twice daily in each eye for a 4 week period. Subjects were assessed at follow up (days 5-8) and termination (days 25-31) visits. The primary efficacy variable was the responder rate, based on the subjects' assessment of global efficacy at the follow up visit.. 519 subjects were randomised to treatment. At the follow up visit, the responder rate, based on subjects' assessment of global efficacy, was significantly greater in the ketotifen group (49.5%) than in the placebo group (33.0%) for subjects with a positive diagnostic test for pollen allergy (p = 0.02). The investigators' assessment of responder rates also showed that ketotifen was superior to placebo (p = 0.001). Ketotifen produced a significantly better outcome than levocabastine (p<0.05) for relief of signs and symptoms of SAC, at both the follow up and the termination visit. The type and frequency of adverse events were similar across treatment groups.. In an environmental setting, ketotifen fumarate 0.025% ophthalmic solution was well tolerated and effective in reducing the signs and symptoms of SAC, and in preventing their recurrence. Ketotifen consistently showed the best efficacy in comparison with both placebo and levocabastine. These results indicate that ketotifen eye drops are a valuable treatment option for this condition.

Topics: Anti-Allergic Agents; Conjunctivitis, Allergic; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Ketotifen; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Seasons; Secondary Prevention; Treatment Outcome

To assess the cost effectiveness of emedastine, a new antihistamine, versus levocabastine in the treatment of acute allergic conjunctivitis (AAC) in Belgium, France, Germany, The Netherlands, Norway, Portugal and Sweden.. Randomised double-blind multicountry clinical trial followed by economic modelling from the treatment provider perspective.. A total of 221 patients (109 emedastine, 112 levocabastine) with AAC were included.. The clinical trial compared the efficacy and safety of emedastine 0.05% and levocabastine 0.05%, both twice daily, for 42 days, using ocular redness, itching, days without symptoms and clinical failure as outcome measures. The cost of first-line treatment failure, including visits, drugs and laboratory examinations, was established in each country from a panel of ophthalmologists and general practitioners. Full sensitivity analyses were conducted.. From day 7 to 42, patients treated with emedastine had less itching (p < 0.001) and less redness (p < 0.001). The failure rate was 10% less (p < 0.02) with emedastine and patients treated with emedastine had an incremental 8.5 days (p < 0.01) without symptoms. Emedastine and levocabastine were equally well tolerated. In all European countries, the cost of failure was lower with emedastine. Emedastine was found to be economically dominant relative to levocabastine, i.e. more effective and less expensive, in Belgium, Germany, Portugal and Sweden; in France, The Netherlands and Norway the incremental cost was low (less than 1 euro per additional symptom-free day).. Through a model based on a randomised clinical trial and cost estimates of treatment failure derived from practitioner interviews, emedastine is a cost-effective treatment of AAC.

Topics: Benzimidazoles; Conjunctivitis, Allergic; Cost-Benefit Analysis; Double-Blind Method; Health Care Costs; Histamine H1 Antagonists; Humans; Piperidines

The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H(1) antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis.. In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed.. Both emedastine and levocabastine produced a statistically significant (P =.0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P <.006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis.. Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Child; Child, Preschool; Conjunctivitis, Allergic; Double-Blind Method; Drug Administration Schedule; Female; Histamine H1 Antagonists; Humans; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pruritus

Nedocromil sodium and levocabastine are widely used for the treatment of ocular allergy, but their mechanisms of action are unclear.. We sought to compare the efficacy and mechanisms of action of nedocromil sodium and levocabastine in reducing conjunctival symptoms after ocular allergen challenge.. We performed a double-blind, placebo-controlled study in which 48 subjects were randomized to 3 groups to receive nedocromil sodium (2%), levocabastine (0.05%), or placebo eye drops twice daily for 2 weeks before ocular challenge with 10 microL of ryegrass extract. Symptoms and tear histamine and PGD(2) concentrations were determined before challenge and at 10, 20, 30, 60, 180, and 360 minutes after challenge. Bulbar biopsy specimens were taken at 6 and 24 hours after challenge to assess conjunctival inflammatory cell numbers, adhesion molecule expression, and mast cell-associated IL-4, IL-5, IL-6, IL-13, and TNF-alpha levels.. Both drugs significantly reduced total symptom scores (P <.05) at all times after challenge compared with placebo. Itching, hyperemia, and lacrimation were most affected. Nedocromil sodium treatment reduced tear concentrations of histamine (by 77%) and PGD(2) (by 70%) at 30 minutes after challenge (both P <.05). In biopsy specimens nedocromil sodium reduced the number of 3H4-positive mast cells (purportedly the secreted form of IL-4) by 49% at 6 hours and 59% at 24 hours (both P <.05). Levocabastine reduced intercellular adhesion molecule 1 expression by 52% at 6 hours and 45% at 24 hours (both P <.05).. Nedocromil sodium and levocabastine both reduced the conjunctival symptoms after ocular allergen challenge but appeared to work by different mechanisms. Nedocromil sodium reduced mast cell function, whereas levocabastine appeared to have primarily antihistaminic actions, although it also reduced the expression of intercellular adhesion molecule 1.

Topics: Adult; Anti-Allergic Agents; Conjunctiva; Conjunctivitis, Allergic; E-Selectin; Female; Histamine; Histamine H1 Antagonists; Humans; Intercellular Adhesion Molecule-1; Lolium; Male; Middle Aged; Nedocromil; Piperidines; Prostaglandin D2; Tears; Vascular Cell Adhesion Molecule-1

To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects.. In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3-16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days.. Overall results showed both drugs have an effect and that emedastine was significantly superior (p < 0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p < 0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42.. These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.

Topics: Adolescent; Benzimidazoles; Child; Child, Preschool; Conjunctivitis, Allergic; Double-Blind Method; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Safety; Suspensions

To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis.. In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model.. At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p < 0.05). A statistical trend was seen at Day 3 (0.05 < p < 0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p < 0.05).. Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Child; Child, Preschool; Conjunctiva; Conjunctivitis, Allergic; Double-Blind Method; Edema; Eyelid Diseases; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Safety; Seasons; Treatment Outcome

To compare a new ocular antihistamine, emedastine difumarate (Emadine Ophthalmic Solution 0.05%; Alcon Laboratories, Fort Worth, Texas), with the marketed ocular antihistamine, levocabastine hydrochloride (Livostin Ophthalmic Suspension 0.05%; CIBA Vision, Atlanta, Georgia), in the treatment of allergic conjunctivitis after conjunctival allergen challenge.. We performed a prospective, double-masked, randomized, contralateral eye study comparing emedastine 0.05% in one eye with levocabastine 0. 05% or emedastine vehicle (placebo) in the contralateral eye. Efficacy was determined 10 minutes and 2 hours after administration of study medications. Ocular itching and redness scores were recorded 3, 5, and 10 minutes after conjunctival allergen challenge.. A total of 97 subjects with a history of allergic conjunctivitis and a positive response to a diagnostic test were evaluable for safety analysis, and 91 subjects were evaluable for the efficacy analysis. Emadastine 0.05% was statistically significantly more effective than levocabastine 0.05% in reducing ocular itching after conjunctival allergen challenge in both the 10-minute and the 2-hour challenge (P <.05). Emedastine 0.05% and levocabastine 0.05% were statistically equivalent in reducing conjunctival redness after conjunctival allergen challenge, although emedastine tended to be more efficacious than levocabastine at every observation time point.. After conjunctival allergen challenge, emadastine 0.05% is significantly more effective than levocabastine 0.05% in reducing ocular itching associated with allergic conjunctivitis. The two compounds are equivalent in controlling the conjunctival redness associated with allergic conjunctivitis.

Topics: Adolescent; Adult; Aged; Allergens; Benzimidazoles; Conjunctiva; Conjunctivitis, Allergic; Double-Blind Method; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Safety; Suspensions; Treatment Outcome

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients' diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastine-treated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Conjunctivitis, Allergic; Consumer Product Safety; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Medical Records; Middle Aged; Ophthalmic Solutions; Phthalazines; Piperidines; Time Factors

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

The authors present the result of an open controlled trial of the effectiveness of a new antiallergic ophthalmological preparation, Livostin, for local use, a product of Janssen-CILAG. They evaluate the results obtained in 86 patients with symptoms of allergic conjunctivitis. The preparation was followed up for four weeks, in particular the rate of onset of effect and its duration. Evidence was provided that this preparation is a highly effective local antiallergic drug with a long-term effect.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines

Allergic conjunctivitis is one of the most frequent allergic diseases of the anterior eye segment.. This multicentre, clinical trial was an investigation to compare the antiallergic efficacy, local tolerance and safety of Antazolin/Tetryzolin eye drops and Levocabastine eye drops. 69 patients were treated over a 2 weeks course of therapy. The subjective and objective ocular symptoms were documented over the treatment period.. Both eye drops reduced subjective and objective ocular symptoms effective. The difference between the treatments (p = 0.0395) was the faster onset of action of Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial medication.. A fast and effective onset of action is of high clinical relevance. Therefore the benefits of using Antazolin/Tetryzolin eye drops was clearly outweigh.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antazoline; Anti-Allergic Agents; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Nasal Decongestants; Ophthalmic Solutions; Piperidines

Multiple ocular challenges or seasonal trials have demonstrated the efficacy of levocabastine and nedocromil sodium in the treatment of allergic conjunctivitis.. This study was designed to compare the protective effect of levocabastine eye drops with that of nedocromil in a conjunctival provocation test with allergen.. Twenty-four patients with allergic conjunctivitis to grass pollen were recruited. After a preliminary provocation to determine conjunctival reaction threshold (erythema of at least 50% of the conjunctiva with ocular itching), patients were randomized to receive either topical levocabastine (0.05%) or nedocromil (2%) 15 minutes before provocation. Erythema and pruritus intensity were recorded at each concentration of allergen up to the reaction threshold.. The allergen concentration level necessary to reach reaction threshold was increased (p < 0.001) after treatment with both drugs. Comparison between screening and each treatment indicated that the shift in allergen concentration was significantly greater after levocabastine treatment than after nedocromil treatment (p = 0.019). Conjunctival itching (symptom score) and erythema (percent conjunctival surface) were also better controlled by levocabastine than by nedocromil during provocation (p < 0.05).. In a provocation test with allergen, levocabastine and nedocromil were both effective in increasing the conjunctival tolerance to allergen, with better protection provided by levocabastine.

Topics: Administration, Topical; Adolescent; Adult; Allergens; Conjunctiva; Conjunctivitis, Allergic; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Immune Tolerance; Male; Middle Aged; Nedocromil; Piperidines; Pollen

Ebastine is H1 receptor antagonist, powerful and selective for histamine. Its efficacy has been evaluated in control of symptoms of persistent rhinitis, appearance of secondary effects and tolerance of the drug, in 30 children who were suffering from persistent rhinitis, of which the diagnosis included:- clinical history, skin tests (prick test) nasal and conjunctival provocation tests, total and specific IgE. All the children had treatment for 30 days. The parameters followed were:- clinical score, skin tests, nasal and conjunctival provocations and evaluation of secondary effects, of the start and 10 days after the end of treatment. The results obtained were a disappearance or reduction of the weals from histamine and specific antigens, disappearance or reduction of the response in nasal and conjunctival provocation with carbachol or specific antigens, clear clinical improvement in 22 patients, in 2 small improvement and no response in 6 patients. We conclude that Ebastine improved the clinical symptoms in persistent rhinitis, the skin test is inhibited and sensitivity of the shock organ is reduced. No secondary effects were seen on the Central Nervous System (SNC) and the tolerance of the drug was very good.

Topics: Adolescent; Butyrophenones; Carbachol; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Perennial; Skin Tests; Treatment Outcome

This study was conducted to evaluate the efficacy of 0.05% levocabastine compared with 4% cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge.. Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits (n = 50) received placebo in one eye and cromolyn in the fellow eye, four times daily for 2 weeks. On day 18, subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye. Subjects were challenged and evaluated after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and evaluated after 3, 5, and 10 minutes.. Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05).. These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours.

Topics: Allergens; Conjunctivitis, Allergic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Models, Biological; Ophthalmic Solutions; Piperidines

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

The efficacy and tolerability of levocabastine eye drops in vernal conjunctivitis (VC) were evaluated in a double-blind, placebo-controlled trial involving 46 patients over a period of 4 weeks. After 1 week of treatment, therapeutic efficacy was considered to be excellent or good for 70% of the levocabastine-treated patients compared with only 33% of patients in the placebo group (p < 0.009). Levocabastine patients experienced significantly greater relief of their individually severest symptom than placebo-treated patients both after 1 week and at the end of the trial (p < 0.04). The reduction in symptom severity was significantly greater in the levocabastine group than in the control group for photophobia (p < 0.003) after 1 week, and for photophobia (p < 0.008), irritation (p = 0.05) and itchy eyes (p = 0.05) at the end of the trial. The percentage of days on which patients were completely symptom-free was significantly higher in the levocabastine group than in the placebo group (28% versus 4%; p < 0.02). Eight placebo-treated patients withdrew from the trial due to treatment inefficacy compared with only four levocabastine-treated patients (p = 0.013). Two of the three levocabastine, and all five placebo patients who elected to continue on open-label levocabastine had an excellent or good overall response after 1 to 3 weeks of treatment. All reported adverse reactions were mild and their incidence was equal in the two treatment groups. Levocabastine eye drops are effective and well tolerated in the treatment of VC.

Topics: Adolescent; Adult; Child; Child, Preschool; Conjunctivitis, Allergic; Double-Blind Method; Drug Tolerance; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prognosis

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

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

The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.

Topics: Adolescent; Adult; Allergens; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Models, Biological; Ophthalmic Solutions; Piperidines

The efficacy, tolerability, and adverse-effect profile of the recently developed, topical antihistamine levocabastine were compared with those of sodium cromoglycate in a 4-week double-blind, placebo-controlled trial in 95 patients with seasonal allergic conjunctivitis. At the end of the trial, global therapeutic efficacy was considered to be excellent or good in 87% of levocabastine-treated patients, as compared with 68% of sodium cromoglycate-treated patients (P = 0.006) and 63% of those who received placebo (P = 0.05). After 4 weeks of treatment, levocabastine patients had experienced significantly greater relief from their most severe ocular symptom than patients in the sodium cromoglycate group (P < 0.05). Furthermore, 37% of levocabastine-treated patients were virtually symptom-free for at least 75% of the treatment period, as compared with only 6% of patients in the sodium cromoglycate group (P < 0.01) and 4% of those who received placebo (P < 0.01). Moreover, this trend was maintained on days when the pollen count was high, when the corresponding figures were 33%, 6% (P = 0.02), and 4% (P = 0.02), respectively. Levocabastine was well tolerated. Indeed, the incidence of adverse reactions was no greater in the levocabastine group than in the placebo group. Topical levocabastine is an effective and well-tolerated drug for the prophylaxis and treatment of seasonal allergic conjunctivitis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Histamine H1 Antagonists; Humans; Middle Aged; Piperidines

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

Levocabastine is a very potent histamine H1 antagonist, available for ocular use as eye drops containing 0.5 mg/ml of levocabastine with benzalkonium chloride as a preservative. Local tolerability of the eye drops was evaluated by objective measurements including slit lamp, tonometry, fluorescein and rose Bengal staining, ophthalmoscopy, visual acuity and visual field determinations, as well as subjectively by questioning for adverse experiences. Seven ocular tolerability studies were performed in a total of 71 volunteers and 103 patients with allergic conjunctivitis. Levocabasine was given from twice to four times daily for 1-8 weeks. Two studies were open, three were placebo controlled and in two, levocabastine was compared with terfenadine. No changes of either clinical or statistical significance were observed in the ocular or peri-ocular tissues. Subjectively, local irritation, pain and tearing were virtually absent. Detailed ophthalmological tolerance studies therefore showed levocabastine eye drops to be very well tolerated.

Topics: Adolescent; Adult; Conjunctivitis, Allergic; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Piperidines; Terfenadine; Visual Acuity

A total of 71 patients with documented birch and grass pollen allergy participated in this randomized, double-blind, parallel-group study initiated to compare the long-term therapeutic efficacy of twice daily levocabastine, a new topical H1-receptor blocker, with that of sodium cromoglycate four times daily in the treatment of pollen-provoked conjunctivitis. There was no statistically significant difference in therapeutic efficacy between the two treatment groups, although a positive trend in favour of levocabastine was observed. Global evaluations of therapeutic efficacy were similar in both treatment groups. A total of 94% of levocabastine-treated patients rated treatment to be excellent or good compared with 86% of patients in the sodium cromoglycate group. Moreover, there were no significant differences in the severity of allergic symptoms reported on the patient diary cards. Patients were permitted to use rescue medication (oral terfenadine and betamethasone nasal spray) if symptoms became severe. The use of rescue medication was lower in the levocabastine group than in the sodium cromoglycate group. The mean number of days on which rescue medication was used was 12.8 and 26.9 in the two groups, respectively. The incidence, and type, of adverse reactions was similar in both patient groups. Levocabastine is well-tolerated and at least as effective as sodium cromoglycate in the treatment of pollen-provoked conjunctivitis.

Topics: Administration, Topical; Adult; Allergens; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Histamine H1 Antagonists; Humans; Longitudinal Studies; Middle Aged; Ophthalmic Solutions; Piperidines; Pollen

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

Levocabastine is a recently developed, potent H1-receptor blocker intended for topical application. Seventeen healthy non-atopic volunteers participated in this randomized, double-blind, placebo-controlled study undertaken to investigate the speed of onset of action, efficacy and tolerability of levocabastine eye-drops after a histamine challenge. The degree of histamine-induced ocular inflammation was found to be significantly less after administration of levocabastine compared with placebo. Furthermore, levocabastine was shown to be rapidly effective with an onset of action within 10 min. Levocabastine eye-drops were well-tolerated and no adverse reactions to the study drug were reported. Levocabastine eye-drops appear to be a valuable therapeutic approach for the treatment of histamine-mediated ocular allergies.

Topics: Adult; Animals; Chick Embryo; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Severity of Illness Index; Time Factors; Treatment Outcome

The aim of this prospective, open study was to evaluate the efficacy and tolerance of the Levocabastine eye drops in daily practice. 273 patients with allergic (rhino)conjunctivitis were treated during 2 weeks. Objective findings and subjective assessments made by the patients were analyzed. The global efficacy was evaluated by the investigator as good or excellent in 73.8% (eye) and 53.6% (nose) of the patients. The results were not age-dependent. The tolerance was scored as good or excellent in 89% of the patients. Less than 6% of the patients stopped the treatment due to intolerance.

Topics: Adult; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Piperidines

Histamine is the key mediator producing itching, redness and chemosis in allergic conjunctivitis. Histamine levels in tears are increased ten-fold in patients with this allergic condition. Levocabastine is a newly synthesized histamine H1 antagonist which has been formulated as both eye drops and nasal spray. In well established assays of antihistamine activity, levocabastine was found to be the most potent antihistamine compound available, being 15,000 times more potent than chlorpheniramine. Ocular provocation studies in man have shown that levocabastine protects against the symptoms of allergen-induced conjunctivitis. Ophthalmological examinations, including slit lamp and ophthalmoscopy showed no adverse effects. Data from therapeutic studies are available for more than 1700 patients with allergic conjunctivitis treated for 2-16 weeks. One drop of levocabastine (0.5 mg/ml) per eye given two to four times daily provided significantly better symptom control than placebo, with good to excellent results in 71% of patients on levocabastine compared to 55% on placebo (p < 0.001). Levocabastine has a fast onset of action. In one study 94% of patients experienced symptom relief within 15 minutes after the first instillation. The effects observed with levocabastine were at least as good as those with ocular cromoglycate or oral terfenadine. The incidence of adverse experiences was not different from placebo. Levocabastine promises to be a valuable treatment for patients with allergic conjunctivitis.

Topics: Animals; Antazoline; Conjunctivitis, Allergic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Naphazoline; Ophthalmic Solutions; Piperidines; Placebos; Terfenadine

Topics: Adolescent; Adult; Cohort Studies; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines

The efficacy and tolerance of topical administration (one drop in each eye q.i.d.) of levocabastine (0.5 mg/ml) was compared with that of sodium cromoglycate (20 mg/ml) and placebo in a 4-week double-blind trial in patients with seasonal allergic conjunctivitis. The investigator rated the treatment as globally good or excellent in significantly more patients treated with levocabastine (89%) than with cromoglycate (67%, P = 0.03) or placebo (48%, P = 0.007). The patients felt that the treatment was more efficacious in 95% (levocabastine), 35% (cromoglycate) and 36% (placebo) of the cases in which they had taken previous antiallergic medication. Total symptom severity according to the patients' diary data was consistently lower with levocabastine than with cromoglycate or placebo for all ocular symptoms. The difference was mainly apparent at the beginning of treatment. The percentage of symptom-free days was higher in the levocabastine group (53%) than in the cromoglycate (31%, P = 0.02) and the placebo group (34%, P = 0.08). Particularly at high-pollen days, levocabastine was superior to cromoglycate in eliminating moderate or severe symptoms. Adverse effects did not occur more frequently with levocabastine or cromoglycate than with placebo. It is concluded that levocabastine is an efficacious, fast-acting and well-tolerated drug in the management of seasonal allergic conjunctivitis.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Histamine H1 Antagonists; Humans; Middle Aged; Ophthalmic Solutions; Piperidines

Levocabastine is a new H1 receptor blocking antihistamine which is intended for topical use in the treatment of allergic conjunctivitis. The protective effect of the drug in conjunctival provocation test (CPT) was evaluated in a double blind study of 25 children aged 9-17 years with confirmed pollen allergy. One drop of levocabastine, cromoglycate or placebo was instilled into the conjunctival sac of both eyes. After 15 min CPT was performed, starting with 320 BU of pollen extract. The allergen dose was increased every 10 min in half 10-log steps in the right eye until a positive reaction occurred, or the top dose 320,000 BU was reached. The lowest dose resulting in a positive CPT reaction, i.e. at least 50% of the conjunctiva with erythema, was defined as the allergenic threshold dose (ATD). Pretreatment with levocabastine resulted in a median ATD of 32,000 BU, compared with 10,000 after cromoglycate (P less than 0.001) or placebo (P less than 0.01). Levocabastine was also superior in reducing subjective itch in the eyes. Determination of the ATD can be used as a relatively quick assessment of drugs intended for the treatment of allergic conjunctivitis.

Topics: Adolescent; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Ophthalmic Solutions; Piperidines; Pollen; Random Allocation

Thirty patients with allergic conjunctivitis, caused by Parietaria or grass pollens, participated in a double-blind parallel study comparing levocabastine to cromolyn sodium, both given as eye drops. Symptom and sign scores were recorded during a 4-week period. The patients received only these drugs during the time of observation. The evaluation of the clinical signs and symptoms by the clinicians and by the patients revealed a significant improvement of conjunctivitis in all patients. The intergroup comparison was equal in the two groups treated respectively with levocabastine and cromolyn. Therefore, levocabastine and cromolyn are effective in the treatment of pollen-induced allergic conjunctivitis.

Topics: Administration, Topical; Adolescent; Adult; Clinical Trials as Topic; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Pollen

The aim of this study was to evaluate the effect of levocabastine, a new H1-blocking antihistamine for topical use, in comparison with sodium cromoglycate on conjunctival symptoms of birch pollinosis. The two drugs were compared in a randomized double-blind comparative study over 5 weeks in 37 children and adolescents (6-19 years of age) with birch pollen conjunctivitis. Nasal symptoms occurred in 31 of the children and were treated with beclomethasone dipropionate nasal spray. An oral antihistamine was offered as rescue medication for eye symptoms. Initially, the patients received placebo four times a day for a 7-day run-in period. Conjunctival symptoms were recorded daily on diary cards on a 100 mm visual analogue scale. The pollen counts indicated a short but intensive birch pollen season. There was no statistically significant difference between the two treatment groups with regard to eye symptom scores before and during active treatment. However, the patients' evaluation of the efficacy of the therapy was in favour of levocabastine (P less than 0.01). Topical levocabastine, an H1-blocker, applied twice daily, seems to protect from symptoms of allergic conjunctivities as favourably as sodium cromoglycate applied four times a day. There was no difference in number or character of reported adverse reactions between the two treatment groups.

Topics: Adolescent; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Pollen; Randomized Controlled Trials as Topic

Levocabastine is a new, highly potent, and specific H1 antagonist. The effects of this drug, administered topically, were evaluated in a conjunctival provocation test (CPT) with allergens. CPT was performed by the instillation of one drop of allergen at increasing concentrations in the inferior conjunctival sac of each eye, alternatively, and stopped when both itching and redness of the conjunctiva were present. The concentration of allergen at this step was considered as the reaction threshold. Eleven patients, allergic to grass pollen, underwent, in winter, a first CPT without pretreatment (screening test); the CPT was then repeated twice after a 24-hour treatment, once, with a placebo, and once, with levocabastine (one drop twice a day, 0.5 mg/ml), administered in a double-blind fashion and in random order. The minimal interval between the two tests was 1 week. There was no significant difference between the thresholds determined in the two CPTs performed without medication (screening test and placebo), whereas the threshold was significantly increased (p less than 0.001) after pretreatment with levocabastine. Individually, the threshold increased in 10/11 patients (p less than 0.01). Levocabastine prevented both redness and itching. A late allergic reaction was observed by the patient in 6/11 CPTs performed after placebo treatment and 8/11 after levocabastine treatment. We conclude that, in this model of allergic conjunctivitis, levocabastine increased the conjunctival tolerance to an allergen. Further studies should help to determine the true place of this H1 antagonist in the treatment of allergic conjunctivitis.

Topics: Allergens; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Immunologic; Female; Histamine H1 Antagonists; Humans; Male; Piperidines

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

Forty patients suffering from allergic conjunctivitis, due to birch pollen, participated in a double-blind parallel group comparison between levocabastine (a potent new specific histamine (H1) antagonist) and placebo, both given as eye drops. Symptom scores were recorded during a 4-week period. A 1-week run-in period was followed by a 3-week treatment period. To enable a fair evaluation of the treatment effect on the ocular symptoms only, all patients were treated with topical nasal glucocorticoids for possible rhinitis symptoms during the whole study period. Plasma levels of levocabastine were determined in all subjects at the end of the 3 weeks' treatment period. Pollen counts for birch pollen were followed simultaneously. The evaluation of the symptom score cards revealed a significant reduction of ocular symptoms following use of the active compound. The resorption of the active substance through the conjunctiva was low. In accordance with the present trend of more topical treatment for allergic rhinitis, levocabastine may constitute a valuable compound for the topical treatment of allergic conjunctivitis.

Topics: Adolescent; Adult; Clinical Trials as Topic; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines

Topics: Computer Simulation; Conjunctivitis, Allergic; Gas Chromatography-Mass Spectrometry; Humans; Photolysis; Piperidines; Pyridines

Allergic conjunctivitis (AC), a common eye inflammation that affects patients' health and quality of life, is still a therapeutic challenge for ophthalmologists. Tofacitinib, a new Janus kinase (JAK) inhibitor, has been successfully used in the treatment of several disorders. Nonetheless, its effect in AC and the potential anti-allergic mechanisms are still unclear. The objective of the current study was to explore the roles of tofacitinib in preventing AC and elucidate the potential underlying mechanisms.. Tofacitinib was used topically in BALB/c mice with experimental allergic conjunctivitis (EAC). Ocular allergic symptoms and biological modifications were examined. To assess the anti-allergic mechanisms of tofacitinib, RBL-2H3 cells and HUVECs were cultured in vitro. The inhibitory effects and mechanisms of tofacitinib were studied and measured by real-time quantitative PCR, ELISA, western blot analysis, and flow cytometry.. Topical administration of tofacitinib reduced the clinical symptoms of OVA-induced EAC, with a substantial mitigation in inflammatory cell infiltration, histamine release, and TNF-α mRNA as well as IL-4 mRNA expression. In vitro, tofacitinib repressed the degranulation and cytokine production in RBL-2H3 cells and reduced histamine-induced vascular hyperpermeability. The underlying mechanism might involve the downregulation of phosphorylation of JAK3/STATs signaling molecules in RBL-2H3 cells and HUVECs.. Our findings provide evidence that tofacitinib prevented EAC by targeting the JAK3/STATs pathway. We recommend the use of tofacitinib as an innovative approach for the treatment of AC.

Topics: Allergens; Animals; Anti-Allergic Agents; Cell Degranulation; Cell Line; Conjunctivitis, Allergic; Disease Models, Animal; Female; Humans; Immunosuppression Therapy; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Piperidines; Pyrimidines; Rats; Signal Transduction; Tumor Necrosis Factor-alpha

Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo.. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed.. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria.. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine.. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Topics: Aged; Aged, 80 and over; Benzimidazoles; Conjunctivitis, Allergic; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Incidence; Male; Piperidines; Prospective Studies; Rhinitis, Allergic; Spain; Urticaria

To evaluate ocular surface temperature in assessing the efficacy of anti-allergic eye drops.. Thirteen asymptomatic patients (24.7 ± 2.8 years) with proven seasonal allergic conjunctivitis due to cedar pollen were studied. A 0.025% levocabastine ophthalmic suspension was instilled in one eye (levocabastine eye) and artificial tears in the other eye (artificial tear eye) in a masked fashion 10 min prior to a conjunctival allergen challenge (CAC). Then, a drop of cedar pollen solution was dropped into the conjunctival sac to induce the allergic reaction. The surface temperature of the inferior bulbar conjunctiva was measured before and 30 min after the CAC with a newly developed non-contact ocular surface thermographer (OST). The degree of conjunctival injection and chemosis was also determined by slit-lamp biomicroscopy. The changes in the symptoms were evaluated by a questionnaire.. After the CAC, the temperature increased by 0.67 ± 0.10°C in the artificial tear eyes but by only 0.21 ± 0.06°C in the levocabastine eyes (p < 0.05). The score for conjunctival injection was 1.38 ± 0.24 and the chemosis score was 0.85 ± 0.25 for the artificial tear eyes and 0.62 ± 0.27 and 0.08 ± 0.08 in the levocabastine eyes (p < 0.01). The temperature increase was significantly correlated with the conjunctival injection scores (r = 0.63; p < 0.001).. The significant correlation of the conjunctival surface temperature with the severity of the conjunctival allergic reaction indicates that the temperature measured by the OST can be used to objectively evaluate the efficacy of topical anti-allergic agents.

Topics: Adult; Allergens; Body Temperature; Conjunctiva; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Ophthalmic Solutions; Piperidines; Thermography; Young Adult

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Topics: Administration, Oral; Benzimidazoles; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

Topics: Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists; Humans; Piperidines

To elucidate the ocular pharmacological properties of bepotastine besilate, a selective histamine H(1) receptor antagonist, when compared with other histamine H(1) receptor antagonists, using guinea pig allergic conjunctivitis models and in vitro models of eosinophil recruitment and mast cell membrane stabilization. Conjunctival vascular hyperpermeability was studied in guinea pigs passively sensitized with anti-ovalbumin antiserum or following subconjunctival injection of histamine. Modulation of eosinophil recruitment was evaluated for both platelet-activating factor (PAF)-induced eosinophil infiltration in guinea pigs and leukotriene B(4)-induced in vitro chemotaxis of guinea pig peritoneal eosinophils. Membrane-stabilizing effects of bepotastine also were studied with rat peritoneal mast cells stimulated with the ionophore A23187. Histamine H(1) receptor antagonists including bepotastine besilate were topically administered before ovalbumin, histamine or PAF challenges for in vivo experiments or were added directly to mast cell and eosinophil medium in vitro. Bepotastine besilate significantly inhibited conjunctival vascular hyperpermeability in a dose-dependent manner with maximal effect for bepotastine besilate 1.5%. In separate in vivo experiments, bepotastine besilate 1.0% was significantly more effective than levocabastine 0.025% in the passive sensitization model or olopatadine 0.1% in the histamine-induced hyperpermeability model. Bepotastine besilate 1.0% further suppressed PAF-induced eosinophil infiltration into conjunctival tissue more effectively than ketotifen 0.05%. Chemotaxis of guinea pig peritoneal eosinophils and histamine release from rat peritoneal mast cells in vitro were also inhibited by addition of bepotastine. Olopatadine had a weak effect as compared to that of bepotastine on eosinophil chemotaxis and no effect on mast cell histamine release in our study conditions. Bepotastine besilate was more potent than olopatadine, ketotifen, or levocabastine in reducing vascular hyperpermeability in various animal models of allergic conjunctivitis. Mast cell function and eosinophil chemotaxis were also inhibited in vitro with bepotastine, suggesting bepotastine acts as an inhibitor of allergic response through multiple mechanisms: histamine H(1) receptor antagonism, mast cell stabilization, and inhibition of eosinophil migration to ocular inflammatory sites.

Topics: Animals; Capillary Permeability; Cells, Cultured; Chemotaxis, Leukocyte; Conjunctiva; Conjunctivitis, Allergic; Disease Models, Animal; Dose-Response Relationship, Drug; Eosinophils; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine Release; Leukotriene B4; Male; Mast Cells; Ovalbumin; Peritoneal Cavity; Piperidines; Platelet Activating Factor; Pyridines; Rats; Rats, Wistar

Six allergic conjunctivitis patients (12 eyes) and 4 healthy volunteers (8 eyes) were investigated in terms of the effect of cooling sheets on eye itching and tear histamine concentration, before and 5 min after cooling the eyelids with cooling sheets. The severity of itching was evaluated with a five-level itching score. The combination treatment of levocabastine with cooling sheets significantly reduced eye itching, while no significant change in tear histamine concentration was observed before and after cooling sheet use. The cooling sheets are useful for reducing eye itching in the therapy of allergic conjunctivitis. The tear histamine concentration did not correlate with the antiitching effect of cooling sheets in this study.

Topics: Conjunctivitis, Allergic; Cryotherapy; Enzyme-Linked Immunosorbent Assay; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Ophthalmic Solutions; Piperidines; Pruritus; Severity of Illness Index; Tears

To characterize the transcriptome of allergic conjunctivitis mediated by eosinophil-related chemokine receptor CCR3 and to identify a candidate for possible therapeutic intervention in eosinophilic inflammation of the eye.. Mice were sensitized to ragweed pollen, and allergic conjunctivitis was induced by an allergen challenge. The induction of allergic conjunctivitis was used to determine whether an inhibition of CCR3 would suppress eosinophilic inflammation and the allergen-induced immediate hypersensitivity reaction. In addition, sensitized mice were treated with a CCR3 antagonist or an anti-CCR3 antibody before the allergen challenge. Eosinophilic inflammation was evaluated histologically at 24 hours after the allergen challenge. Transcriptional changes with or without a blockade of CCR3 were determined by microarray analyses.. Blockade of CCR3 significantly suppressed allergen-induced clinical signs, mast cell degranulation, and eosinophilic inflammation. Clustering analysis of the transcriptome during the early phase identified clusters of genes associated with distinct biological processes. A CCR2 ligand, monocyte chemoattractant protein (MCP)-1, was identified in the cluster of genes related to mast cell activation. MCP-1, an attractant of monocytes but not eosinophils, was in the top 10 transcripts among the genome and was suppressed by CCR3 blockade. Importantly, antibody blockade of MCP-1 suppressed the eosinophilic inflammation significantly.. CCR3 regulates not only the eosinophilic inflammation but also the clinical signs and mast cell degranulation. The CCR3-mediated transcriptome is characterized by many biological processes associated with mast cell activation. Among these CCR3-mediated processes, MCP-1 was found to be significantly involved in eosinophilic inflammation probably by an indirect pathway.

Topics: Ambrosia; Animals; Capillary Permeability; Cell Degranulation; Cell Movement; Chemokine CCL2; Conjunctivitis, Allergic; Disease Models, Animal; Eosinophils; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin G; Mast Cells; Mice; Mice, Inbred Strains; Oligonucleotide Array Sequence Analysis; Piperidines; Pollen; Receptors, CCR3; Transcription, Genetic

We investigated the early efficacy of topical levocabastine, an H(1) histamine-receptor antagonist, in improving the clinical symptoms of allergic conjunctivitis.. Thirty-six patients with allergic conjunctivitis were enrolled. One drop of levocabastine was instilled in one eye and one drop of artificial tears in the contralateral eye. Clinical examinations were performed before, and 15 and 30 minutes after instillation. Symptoms of itching and signs of injection were assessed at each time point.. Both levocabastine and artificial tears resulted in a statistically significant reduction in ocular itching. However, levocabastine was significantly more effective.. Although artificial tears had a positive effect in reducing symptoms of allergic conjunctivitis, by the washing out of allergens, levocabastine was more effective than artificial tears in controlling acute symptoms of allergic conjunctivitis, demonstrating that the selective H1 histamine-receptor antagonist action of levocabastine is rapidly effective in a clinical setting.

Topics: Administration, Topical; Adult; Aged; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Treatment Outcome

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

The effect of the simultaneous use of 0.025% levocabastine hydrochloride eye drops (levocabastine) and 0.1% pemirolast potassium ophthalmic solution (pemirolast) on experimental allergic conjunctivitis in rats was investigated. Levocabastine and pemirolast significantly inhibited allergic conjunctivitis compared with the control group when separately administered. In addition, the simultaneous use of both drugs inhibited allergic conjunctivitis more potently than the original activity of levocabastine or pemirolast. Furthermore, the simultaneous use of levocabastine and pemirolast also significantly inhibited increased vascular permeability induced by antigen compared with levocabastine or pemirolast alone, respectively. Levocabastine and pemirolast inhibited histamine release from the rat conjunctiva in correlation with a decrease in histamine content in tears. When levocabastine and pemirolast were simultaneously applied to the eyes, histamine release from the conjunctiva was greater than for the original activities of both drugs. Similar to histamine release from the conjunctiva, the histamine content in tears induced by the simultaneous use of both drugs was significantly decreased compared with levocabastine and pemirolast alone, respectively. A potentiating effect induced by the simultaneous use of levocabastine and pemirolast may be attributable to the antihistaminic activity of levocabastine and histamine release inhibition by levocabastine and pemirolast.

Topics: Animals; Conjunctivitis, Allergic; Drug Synergism; Drug Therapy, Combination; Histamine Release; Male; Piperidines; Pyridines; Pyrimidinones; Rats; Rats, Wistar

To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats.. Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control.. At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine.. In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.

Topics: Anaphylaxis; Animals; Capillary Permeability; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Edema; Eyelids; Guinea Pigs; Histamine H1 Antagonists; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Ovalbumin; Piperidines; Rats

(1) There is no clearly established reference eye-drop preparation for the treatment of allergic conjunctivitis. Steroid eye drops must be avoided. Virtually the only criterion on which to base the choice among the other antiallergic eye drops is the type and presence of preservatives, as these must be avoided by the small number of patients who are allergic to them. (2) In our opinion the clinical file on the 0.05% emedastine eye drops now available in France fails to answer many practical questions, as it almost solely comprises single-dose clinical pharmacology studies. (3) A trial involving 221 patients with allergic conjunctivitis, during a period of pollination, showed no tangible difference in efficacy between 0.05% emedastine and 0.05% levocabastine eye drops after 6 weeks of treatment. (4) The main adverse effects observed in clinical trials were local, consisting of eye redness, dryness and discomfort. When taken orally, emedastine is known to prolong the QT interval, and it is difficult to determine the precise cardiac risk during ocular administration. (5) 0.05% emedastine eye drops change nothing in the management of allergic conjunctivitis.

Topics: Anti-Allergic Agents; Benzimidazoles; Clinical Trials as Topic; Conjunctivitis, Allergic; France; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines; Treatment Outcome

Topics: Anti-Allergic Agents; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Nedocromil; Piperidines; Rhinitis, Allergic, Perennial

Topics: Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Drug Combinations; Histamine H1 Antagonists; Humans; Ketorolac Tromethamine; Ophthalmic Solutions; Oxamic Acid; Piperidines; Tolmetin; Tromethamine

Topics: Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Piperidines

Topics: Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Oxamic Acid; Piperidines; United States; United States Food and Drug Administration

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

Levocabastine, selected from a series of cyclohexylpiperidine derivatives protects rats from compound 48/80-induced anaphylactic shock for at least 16 h at the oral dose of 0.0015 mg/kg. At the same dose histamine skin reactions and at slightly higher doses passive cutaneous anaphylactic reactions are inhibited. Blockade of passive cutaneous anaphylactic reactions is obtained with levocabastine, despite absence of peripheral serotonin antagonism and any other known non-specific action that may facilitate inhibition of passive anaphylaxis. In dogs allergic reactions are inhibited at oral doses 40 times lower than ketotifen. In guinea-pigs orally and topically administered levocabastine are remarkably effective against allergic conjunctivitis.

Topics: Anaphylaxis; Animals; Ascaris; Conjunctivitis, Allergic; Dogs; Guinea Pigs; Histamine; Histamine H1 Antagonists; Hypersensitivity; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Piperidines; Rats

The effect of levocabastine on allergic and histamine (Hi)-induced conjunctivitis in guinea pigs was compared with those of cromolyn sodium and amlexanox. Levocabastine inhibited both antigen- and Hi-induced conjunctivitis. Amlexanox had no effect on Hi-induced conjunctivitis; however, the drug elicited a significant inhibition of allergic conjunctivitis. On the other hand, the effect of cromolyn sodium was almost negligible in both cases. Levocabastine moderately inhibited Hi release from guinea pig conjunctiva induced by antigen-antibody reactions. Amlexanox also caused a significant inhibitory effect, whereas cromolyn sodium was not effective in suppressing Hi release induced by antigen challenge. Furthermore, levocabastine prevented an increase in the vascular permeability elicited by both Hi and antigen instillation.

Topics: Aminopyridines; Animals; Antigens; Capillary Permeability; Conjunctivitis, Allergic; Cromolyn Sodium; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine Release; Histidine Decarboxylase; Male; Piperidines; SRS-A

The efficacy of a new antihistamine, levocabastine, in alleviating the ocular allergic reactions induced by both histamine and 48/80 was evaluated in humans. Levocabastine (0.5%) was instilled in one eye of 30 volunteers, and vehicle in the contralateral eye. After 15 minutes, half of the subjects received histamine (25 mg/ml) and half, 48/80 (7.5 mg/ml). The signs and symptoms of allergy were graded clinically after 30 minutes. Compared with a buffer control, levocabastine significantly alleviated itching (P = 0.01), redness (P = 0.0156), and chemosis (P = 0.005) induced by histamine, and itching (P = 0.032) and redness (P = 0.029) induced by 48/80. The results from these pharmacologic models support the clinical use of levocabastine for the treatment of allergic conjunctivitis.

Topics: Conjunctivitis, Allergic; Histamine; Humans; p-Methoxy-N-methylphenethylamine; Piperidines

In an animal model, topical application of levocabastine to the eye inhibits the inflammatory conjunctival response to topically applied histamine. This is so even at one-fourth the concentration at which levocabastine is normally dispensed. Total blocking of histamine response continues for 24 h and is then irregularly observable for an additional 72 h. Levocabastine may be absorbed through the conjunctiva to give systemically transmitted protection to the contralateral eye. Levocabastine is a potent competitor against histamine for conjunctival H1 receptors and should prove a useful, possibly long-acting drug for the reversal of inflammatory conjunctivitis and inhibition of its recurrence.

Topics: Administration, Topical; Animals; Conjunctivitis, Allergic; Drug Evaluation, Preclinical; Guinea Pigs; Histamine; Histamine H1 Antagonists; Piperidines