Comparison of the efficacy and tolerability of topically administered azelastine,sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis

SUMMARY

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study.

Research design: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion.

Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period.

Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale.

Results: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p?=?0.005; sodium cromoglycate p?=?0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion.

Conclusion: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.     

Topical azelastine in perennial allergic conjunctivitis

OBJECTIVE: 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. Research design and methods: 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. RESULTS: 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. CONCLUSIONS: 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.     

Azelastine eye drops in the treatment of perennial allergic conjunctivitis

Azelastine (CAS 58581-89-8) is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of other mediators of allergic inflammation. The present double-blind study aimed to evaluate azelastine eye drops (Allergodil) in patients with perennial allergic conjunctivitis compared to placebo. A total of 116 patients with an ocular symptoms score for itching and conjunctival redness > or = 3 (0-6 scale) were randomized to twice-daily 0.05% azelastine eye drops treatment (n = 58) or placebo. Patients maintained daily logs and were clinically evaluated after 7, 21 and 42 days of treatment. Azelastine significantly improved itching and conjunctival redness versus placebo (p < 0.001). Tolerability was rated good or better by 97% of patients with only bitter taste and application site reaction notable adverse experiences. On Day 7, ocular symptoms score improved by 1.5 +/- 0.9 (versus 0.5 +/- 0.8 placebo) with score improvement > or = 2 in 55% with azelastine (versus 14% placebo). Itching and redness further improved at Day 42 (score improvement > or = 2 in 95% with azelastine versus 33% placebo) and completely resolved for 47% azelastine patients (versus 10% placebo). Daily patient logs confirmed the clinically assessed scores. Topical azelastine progressively improved itching and conjunctival redness in patients with moderate to severe perennial allergic conjunctivitis. Continued improvement with prolonged use is consistent with mechanisms other than H1-receptor blockade, such as possible down regulation of adhesion molecule receptors.     

Topical azelastine in perennial allergic conjunctivitis

SUMMARY

Objective: Azelastine is a selective H1-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.

Research design and methods: 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.

Results: 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.

Conclusions: 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 H1-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Azelastine is an antiallergic agent which demonstrates histamine H1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Azelastine antagonises histamine- and leukotriene-induced bronchospasm in animal studies and reduces airway responsiveness to inhaled antigen or distilled water, and exercise challenge. In comparative studies, orally administered azelastine in doses up to 4 mg/day consistently relieved symptoms in patients with seasonal or perennial rhinitis - comparable to inhaled sodium cromoglycate (cromolyn sodium) 80 mg/day, oral chlorpheniramine (chlorphenamine) and oral terfenadine 120 mg/day. In addition, azelastine administered as an intranasal spray was as effective as oral terfenadine 120 mg/day and intranasal budesonide 0.4 mg/day in alleviating symptoms of rhinitis. Azelastine is also a potent antiasthmatic agent which produces significant and long lasting bronchodilation in patients with bronchial asthma. The drug is superior to placebo and comparable to oral ketotifen 2 mg/day and sustained release theophylline 700 mg/day when administered as a twice daily oral 4 mg dose. Azelastine is generally well tolerated: the most common adverse effects are altered taste perception and drowsiness. Adverse effects are mild and transient and result in withdrawal of treatment in less than 2% of patients. In a comparative study oral azelastine 2 or 4 mg/day produced no more sedation than terfenadine 120 mg/day. Thus, barring unexpected findings with wider clinical use, azelastine offers an effective and well tolerated choice of treatment for patients with allergic rhinitis and/or bronchial asthma, which may be particularly beneficial in patients in whom inhaled drug treatment is contraindicated.     

Meta-analysis of azelastine nasal spray for the treatment of allergic rhinitis

STUDY OBJECTIVE: To systematically review the efficacy of azelastine nasal spray for the treatment of allergic rhinitis. DESIGN: Meta-analysis of published randomized controlled trials reported in English. DATA SOURCE: Published literature from the PubMed-MEDLINE database. PATIENTS: Patients aged at least 12 (United States) or 16 years (Europe) with allergic rhinitis or nonallergic vasomotor rhinitis. MEASUREMENTS AND MAIN RESULTS: A global assessment of efficacy was used to estimate the number needed to treat for azelastine nasal spray compared with placebo or active comparators. The total symptom score was used to compare the effect size between azelastine and placebo. In five comparisons of azelastine and placebo, azelastine was most efficacious, with a summary number needed to treat of 5.0 (95% confidence interval [CI] 3.3-10.0). In reviewing 11 studies of azelastine versus active comparators, we found no significant difference between azelastine and active comparators (number needed to treat 66.7, 95% CI 14.3 to infinity to 25). Azelastine was more efficacious than placebo in terms of total symptom score (effect size of 0.36, 95% CI 0.26-0.46). CONCLUSION: Azelastine nasal spray was more efficacious than placebo in the treatment of allergic rhinitis. No significant differences were observed between azelastine and active comparators for the treatment of allergic rhinitis; however, when azelastine was compared with oral antihistamines as monotherapy, the trend favored azelastine. Because azelastine appears to be as efficacious as oral antihistamines, the choice of treatment for seasonal allergic rhinitis should depend on the patient's preference regarding the route of administration, adverse effects, and the cost of the drug.     

Comparison of Azelastine Eye Drops with Levocabastine Eye Drops in the Treatment of Seasonal Allergic Conjunctivitis

Summary

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 levocabastinetreated 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.     

Comparison of azelastine eye drops with levocabastine eye drops in the treatment of seasonal allergic conjunctivitis

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.     

Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: implications for its mode of action

Azelastine is a novel, orally effective, long-acting, antiallergic agent. The ability of azelastine to influence calcium ionophore A23187-induced histamine release from rat peritoneal mast cells was investigated and compared with selected antiallergic drugs. The concentrations of drugs required to inhibit A23187 (0.2 microM)-stimulated histamine release by 50% (IC50S, microM) were as follows: azelastine 5; diphenhydramine 52; and ketotifen 200. Theophylline and sodium cromoglycate in a concentration range of 0.1-1000 microM failed to exert any significant inhibition of histamine release. The inhibitory effects of azelastine on A23187-stimulated histamine release were antagonized by high concentrations of exogenous Ca2+ ions. These data suggest that azelastine inhibits A23187-stimulated histamine release by interfering with the influx of Ca2+ into the mast cells.     

Treatment of atopic eczema in children: clinical trial of 10% sodium cromoglycate ointment.

In a double-blind randomised group-comparative trial 21 children with chronic atopic eczema were treated twice daily for up to 12 weeks with an ointment containing 10% sodium cromoglycate (SCG) in white soft paraffin. A similar group of 21 children was treated for up to 12 weeks with a placebo ointment consisting of the white soft-paraffin base only. The number of patients who withdrew from the trial because treatment was ineffective was significantly greater in the placebo group (16) than in the SCG group (four). Comparison between the two groups also showed significant improvement in inflammation, lichenification, and cracking and the symptoms of itching and sleep disturbance among those on SCG treatment. At the end of treatment significantly more patients in the SCG group (16) had benefited from treatment compared with only two patients in the placebo group. No patients experienced side effects. I conclude that SCG ointment may be a safe alternative to topical steroids in the treatment of atopic eczema in children.     

Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis

OBJECTIVE: The objective of the study was to evaluate the effectiveness of azelastine (Astelin) nasal spray, a topical second-generation antihistamine, in the treatment of symptoms of seasonal allergic rhinitis, seasonal allergic rhinitis with nonallergic triggers (mixed rhinitis), and nonallergic vasomotor rhinitis. RESEARCH DESIGN AND METHODS: A total of 2343 primary care physicians, allergists, ENT specialists, and other health professionals participated in this 2-week, open-label evaluation of azelastine nasal spray. Data were collected through a physician questionnaire that included patient demographics, rhinitis diagnosis, medication history, and inclusion/exclusion criteria; and two patient questionnaires that included symptom history, response to previous rhinitis medications, symptom control, and level of satisfaction with azelastine nasal spray. A completed physician questionnaire and two completed patient questionnaires were required for each patient to be included in the analysis. Patients who qualified for enrollment were given open-label azelastine nasal spray and instructed to administer 2 sprays per nostril twice daily for 2 weeks. RESULTS: A total of 1225 health professionals enrolled 7864 patients into the study. Completed physician and patient questionnaires were returned by 1081 health professionals and 5073 patients, 4364 of whom used azelastine nasal spray as their only rhinitis medication during the 2-week study period. The patients were predominantly caucasian (82.6%) and female (61.1%), with a mean age of 50 years. The majority had a diagnosis of mixed rhinitis (51.5%), followed by seasonal allergic rhinitis (32.3%), and nonallergic (vasomotor) rhinitis (16.2%). After 2 weeks of treatment, the percentage of patients reporting some control or complete control of individual symptoms ranged from 78% for postnasal drip in patients with nonallergic vasomotor rhinitis to 90% for sneezing in patients with seasonal allergic rhinitis. More than 85% of patients who reported difficulty sleeping or impairment of daytime activities due to rhinitis symptoms had improvement in these parameters. Azelastine nasal spray was well tolerated, the discontinuation rate due to adverse events was 2.3%. CONCLUSIONS: Azelastine nasal spray was reported to control all rhinitis symptoms, including nasal congestion, regardless of rhinitis diagnosis during the 2-week study period. Patients with seasonal allergic rhinitis and patients with seasonal allergic rhinitis plus nonallergic triggers were identified as patient types most likely to respond to azelastine nasal spray.     

A study of the clinical efficacy of azelastine in patients with extrinsic asthma, and its effect on airway responsiveness.

1. The effect of 4.4 mg azelastine administered orally on airway responsiveness, skin prick testing, daily peak expiratory flow rates and symptoms of asthma was compared with placebo in a 7 week double-blind, parallel group study of 24 patients with extrinsic asthma. The study was in two parts: a 2 week assessment period, during which all patients received placebo tablets but recorded daily peak flow rates (PEFRs) and symptoms, preceding the 7 week double-blind comparison. 2. Azelastine, 4.4 mg, significantly decreased airway responsiveness to histamine compared with placebo both after a single dose (P less than 0.001), and following 7 weeks continuous treatment (P less than 0.02). Airway responsiveness to methacholine was not altered by administration of azelastine compared with placebo. 3. Skin prick test weal diameters to both allergen and histamine were significantly reduced after both a single dose and following 7 weeks continuous therapy treatment with azelastine. 4. There was a significant improvement in both the mean of the morning and the evening peak flow rates recorded during the last week compared with the first week of the study in the group receiving 4.4 mg of azelastine twice daily compared with placebo. Scores for wheeze were significantly reduced during the final 3 weeks of the study in patients receiving azelastine compared both with those receiving placebo and with the first week of the study (P less than 0.05, P less than 0.01). Consumption of inhaled bronchodilators fell significantly during the study in the group receiving azelastine therapy (P less than 0.05); no such fall occurred in the placebo treated patients. 5. A bitter metallic taste was reported by 58% of patients who received azelastine therapy.     

Levocabastine. A review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergic rhinitis and conjunctivitis.

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.     

Review of azelastine nasal spray in the treatment of allergic and non-allergic rhinitis

Azelastine is a potent H(1)-antihistamine, which is available as a topical nasal spray and indicated for both seasonal allergic and non-allergic vasomotor rhinitis. In addition to its antihistaminic effects, it has also been shown to have a number of other potentially important attributes, including effects on cytokines, adhesion molecules and inflammatory cells. Azelastine nasal spray has been shown to benefit patients who have not responded adequately to loratadine and fexofenadine, and is significantly more efficacious than cetirizine and levocabastine in patients with seasonal allergic rhinitis. Given its unique pharmacologic properties and clinical profile, azelastine maintains an important role in the treatment of chronic rhinitis.     

Comparative efficacy and safety of azelastine and levocabastine nasal sprays in patients with seasonal allergic rhinitis.

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

盐酸氮(卓)司汀与丙酸氟替卡松治疗青少年季节性变应性鼻炎疗效比较

目的 研究盐酸氮(卓)司汀与丙酸氟替卡松治疗青少年季节性变应性鼻炎(SAR)的疗效及安全性.方法 选取2009年3月至2012年3月在我院诊治的SAR青少年患者76例,随机分为盐酸氮(革)司汀组和丙酸氟替卡松组,各38例,分别给予盐酸氮(卓)司汀鼻喷剂和丙酸氟替卡松鼻喷剂治疗,评价2组疗效,并通过鼻部症状总评分(TNSS)和服部症状总评分(TOSS)比较2组临床症状改善情况.结果 盐酸氮革司汀组和丙酸氟替卡松组总有效率分别为76.3％ (29/38)和81.6％ (31/38),组间差异无统计学意义(x2=0.32,P＞0.05).盐酸氮(卓)司汀组治疗前后TNSS分别为(8.7±2.3)分和(5.5±1.6)分,TOSS分别为(6.5±1.8)分和(3.9±1.2)分;丙酸氟替卡松组治疗前后TNSS评分分别为(8.4±2.2)分和(4.6±1.6)分,TOSS分别为(6.6±1.6)分和(4.5±1.3).2组治疗前后TNSS和TOSS的差异均有统计学意义(P＜0.05);治疗后,盐酸氮(卓)司汀组与丙酸氟替卡松组的TNSS和TOSS差异均无统计学意义(P＞0.05).盐酸氮革司汀组有2例患者发生嗜睡,丙酸氟替卡松组1例鼻出血.结论 盐酸氮(草)司汀与丙酸氟替卡松在治疗青少年SAR中均安全有效,二者在改善患者鼻部及眼部症状中效果相似.     

Health economic impact of olopatadine compared to branded and generic sodium cromoglycate in the treatment of seasonal allergic conjunctivitis in the UK

OBJECTIVE: This study estimated the health economic impact of olopatadine (Opatanol) compared to branded cromoglycate (Opticrom) and generic sodium cromoglycate in the treatment of seasonal allergic conjunctivitis (SAC) in the UK. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: A decision model was constructed depicting the management of SAC sufferers who are 4 years of age or above over a typical allergy season of 4 months and considers the decision by a GP to initially treat a patient with olopatadine, branded or generic cromoglycate. The analysis assumed both drugs to be equally effective. Consequently, a cost-minimisation analysis was performed to identify the least costly alternative. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with olopatadine is expected to lead to a healthcare cost of 92 pounds sterling (95% CI: 46 pounds sterling; 150 pounds sterling) over 4 months compared to 109 pounds sterling (95% CI: 65 pounds sterling; 166 pounds sterling) with branded cromoglycate and 95 pounds sterling (95% CI: 51 pounds sterling; 152 pounds sterling) with generic cromoglycate, resulting in a 16% and 3% reduction in healthcare costs respectively over 4 months of treatment. This cost-difference is primarily due to fewer GP visits among olopatadine-treated patients. CONCLUSION: Use of olopatadine instead of branded or generic cromoglycate affords an economic benefit to the NHS. Hence, within the limitations of the model, olopatadine is the preferred first-line treatment for use in SAC sufferers, since it is expected to lead to fewer GP visits, thereby releasing healthcare resources for alternative use.     

Azelastine hydrochloride:a review of pharmacology,pharmacokinetics, clinical efficacy and tolerability

ABSTRACT

Introduction: Azelastine hydrochloride (Astelin) nasal spray 0.1% solution is a second-generation intranasal antihistamine available in the US for treatment of both seasonal allergic rhinitis (SAR) and nonallergic vasomotor rhinitis (VMR).

Scope: Searches of journal articles including the title word ‘azelastine’ from 1979 through the present were conducted by the product manufacturer primarily through Medline and EMBASE but also included, at various times, Dialog, Biosis, Toxline, and Diogenes (an adverse-event database). One limitation of the present review is that it could not exclude the possibility of publication bias, whereby findings from smaller studies and/or trials with negative findings may not have been published.

Findings: Azelastine is a phthalazinone derivative with H₁-receptor binding approximately tenfold greater than chlorpheniramine on a milligram-per-milligram basis. Azelastine has demonstrated a wide range of pharmacologic effects on chemical mediators of inflammation including leukotrienes, kinins, and platelet activating factor in vitro and in vivo. The molecule also has been shown to downregulate intercellular adhesion molecule-1 expression and to reduce inflammatory cell migration in patients with rhinitis. Well-controlled studies in SAR and VMR demonstrated that azelastine nasal spray improves nasal symptoms of rhinitis, including congestion and postnasal drip, and has a rapid onset of action that appears likely due to topical activity. Azelastine nasal spray has demonstrated greater efficacy when used in combination with fluticasone propionate nasal spray when compared to either agent alone, and this combination may provide benefit for patients with moderate-to-severe rhinitis. Bitter taste is the most common side effect associated with azelastine nasal spray and this problem can be mitigated by the dosing technique recommended by the manufacturer in the product labeling. The incidence of somnolence also may be reduced with the recommended administration technique.

Conclusions: Azelastine is an effective, rapid-acting, and well-tolerated second-generation antihistamine that improves nasal symptoms associated with SAR and VMR. Clinical studies demonstrated that azelastine nasal spray can improve symptoms of SAR in patients who remained symptomatic after treatment with oral antihistamines and that azelastine nasal spray in combination with fluticasone nasal spray provided significantly (?p < 0.05) greater relief than either agent alone in patients with SAR.     

Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy

OBJECTIVE: To assess the efficacy and onset of action of azelastine nasal spray and desloratadine tablets in patients with allergen-induced seasonal allergic rhinitis (SAR). RESEARCH DESIGN AND METHODS: 46 adult patients with a history of SAR were exposed to a controlled grass pollen concentration for 6 h in the Vienna Challenge Chamber (VCC) in each treatment period according to a randomised, double-blind (double-dummy), three-period, three-sequence crossover design (wash-out period of 12 days). Single doses of study medication (one puff nasal spray into each nostril of azelastine, 0.2 mg, or placebo before swallowing one encapsulated tablet of desloratadine, 5 mg) were administered 2 h after the start of the allergen challenge. Results of subjective and objective assessments were recorded throughout the challenge. RESULTS: Efficacy of azelastine nasal spray was significantly superior compared to desloratadine tablets (p = 0.005) and placebo (p < 0.001). Desloratadine was significantly better than placebo (p < 0.001). Decrease both in Major Nasal Symptom Score (MNSS) and in Total Nasal Symptom Score (TNSS) was fastest after azelastine treatment. Improvement of nasal symptom severity was most pronounced after azelastine treatment for all nasal symptoms including nasal congestion. Onset of action was 15 min for azelastine compared to 150 min for desloratadine. Both active preparations were safe and well tolerated. CONCLUSIONS: This study confirms the usefulness of azelastine nasal spray for the symptomatic treatment of seasonal allergic rhinitis. Concerning onset of action in particular, the results favour the topical treatment over systemic therapy.     

Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung.

Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways.