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

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

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 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

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.     

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.     

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.     

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.     

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.     

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

SUMMARY

Background: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol*) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat?) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis.

Objective: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model.

Research design and methods: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3?min, 5?min, and 7?min post challenge. Objective redness and chemosis assessments were made at 10?min, 15?min, and 20?min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments.

Main outcome measures; results: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, –0.19 (?p = 0.003) and –0.52 (?p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis –0.24 (?p < 0.001), ciliary redness –0.55 (?p < 0.001), and episcleral redness –0.58 (?p < 0.001) than epinastine treated eyes.

Conclusion: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

* Patanol is a registered tradename of Alcon Laboratories Inc, Forth Worth, TX, USA     

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

ABSTRACT

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 (95% CI: £46; £150) over 4 months compared to £109 (95% CI: £65; £166) with branded cromoglycate and £95 (95% CI: £51; £152) 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.     

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.     

Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge

ABSTRACT

Background: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H₁ antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Objective: To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).

Research design and methods: This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12?h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5?min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4.

Main outcome measures; results: This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7?min and redness was assessed at 7, 15, and 20?min post-challenge. Drop comfort was assessed upon instillation, at 30?s, and at 1, 2, and 5?min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (?p = 0.024) and 7?min (?p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p ≤ 0.013, conjunctival: p ≤ 0.015, episcleral: p ≤ 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1?min post-drop instillation (?p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.

Conclusion: Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.     

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.     

Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease

Sodium cromoglycate stabilizes mast cell membranes and prevents the release of histamine and other biochemical mediators. When topically applied to the eye before allergen exposure, ocular sodium cromoglycate prevents many of the signs and symptoms associated with type I allergic reactions (which includes hayfever, acute allergic and chronic allergic conjunctivitis, and vernal keratoconjunctivitis) and giant papillary conjunctivitis. Although difficulties exist in evaluating clinical trials in allergic eye disease, both open and controlled studies have shown ocular sodium cromoglycate to be very effective in relieving the subjective symptoms and clinical signs of the above ocular disorders. In addition, ocular sodium cromoglycate may decrease the need for supplementary oral antihistamines and, more importantly, the need for ocular corticosteroids, thus decreasing the incidence of steroid-induced ocular side effects. However, in severe cases and in instances of acute exacerbation of symptoms, the combined ocular application of sodium cromoglycate and corticosteroids may be very effective. No systemic or severe adverse reactions have been attributed to ocular sodium cromoglycate, which is not surprising since systemic drug absorption from the eye is minimal. However, transient local stinging and burning have been reported. Thus, although further studies in giant papillary conjunctivitis and comparative studies with corticosteroids in allergic conjunctivitis and vernal keratoconjunctivitis are needed to more clearly define the extent of benefits that may be obtained from ocular sodium cromoglycate, it is clear that the safety and efficacy of the drug in type I allergic eye diseases is such that it should be considered as a first-line agent when drug therapy of these disorders is indicated.     

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.     

Advances in pharmacotherapy for the treatment of allergic rhinitis; MP29-02 (a novel formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) fills the gaps

Introduction: Effective pharmacologic treatment exists for most patients suffering from allergic rhinitis (AR). However, both in clinical trials and in real-life studies, many patients are dissatisfied with treatment. Physicians often use multiple therapies, in an attempt to improve symptom control, often with limited evidence of success. Novel treatment options are needed and must consider unmet medical needs.

Areas covered: This article reviews the clinical data for a new AR treatment. MP29-02 (Dymista®, Meda, Solna, Sweden) contains azelastine hydrochloride (AZE) and fluticasone propionate (FP), in a novel formulation and delivered in an improved device as a single nasal spray. It has shown superior efficacy in AR patients than either commercially available AZE or FP monotherapy for both nasal and ocular symptom relief, regardless of disease severity. MP29-02 also provided more effective and rapid symptom relief than either AZE or FP monotherapy delivered in the MP29-02 formulation and device. However, the effect was less than that observed versus commercial comparators, suggesting the impact of formulation and device on clinical efficacy.

Expert opinion: MP29-02 simplifies AR management, surpassing the efficacy of gold standard treatment, intranasal corticosteroids (INS), for the first time. It is indicated for the treatment of moderate-to-severe seasonal allergic rhinitis and perennial allergic rhinitis when monotherapy with either intranasal antihistamine or INS is NOT considered sufficient. Most patients present with moderate/severe disease, with evidence of current or previous treatment insufficiency. MP29-02 should be the treatment of choice for these patients.     

Comparison of 1 mg and 5 mg sodium cromoglycate metered dose inhalers in the treatment of asthma: A 12-week double-blind,parallel group trial

Summary

A double-blind, parallel group trial of a 1?mg sodium cromoglycate metered dose inhaler, a 5?mg formulation and a placebo aerosol was undertaken in 139 asthmatic patients with extrinsic allergic asthma. None of the patients had previously been treated with sodium cromoglycate and few (15%)were familiar with the use of a pressurized aerosol device. Each test treatment was taken at a dose of 2 ‘puffs’ 4-times per day for a period of 12 weeks. Response to treatment was assessed by analysis of symptom scores, medication usage and 3-times daily home measurements of PEFR recorded on diary cards, and by assessment of asthma severity and lung function in the clinic at the beginning and end of a 2-week baseline period and at intervals of 3 weeks throughout the trial. Analysis of patient-generated data (symptom scores and PEFR)demonstrated statistically significant differences in favour of each active treatment compared with placebo treatment. Clinic assessments of asthma severity and the investigator's opinion of treatment also showed the superiority of each sodium cromoglycate treatment regimen over placebo. These differences were statistically significant after 9 weeks (high dose)and 12 weeks (both doses). No statistically significant differences were demonstrated between the two active treatment groups in the clinic assessments of asthma severity, or in the home or clinic measurements of PEFR. There was, however; a consistent trend in favour of the higher dose formulation with respect to diary card symptom scores. In general, improvement in the low-dose sodium cromoglycate treatment group was slower than in the high-dose group suggesting an advantage for the 5?mg sodium cromoglycate inhaler in terms of onset of therapeutic response. The results indicate that sodium cromoglycate administered by pressurized aerosol at a dose of 2×1?mg or 2×5?mg 4-times daily is effective in the treatment of asthma and suggest that the higher dose formulation may provide more rapid control of symptoms.     

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).     

Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs

The ability of azelastine to inhibit IgE-mediated allergic histamine release from the peritoneal mast cells of actively sensitized rats was investigated and compared with selected antiallergic agents. Azelastine added simultaneously with the allergic stimuli (ovalbumin, OA, 10 micrograms/ml + phosphatidylserine, PS, 10 micrograms/ml) or preincubated with cells for 10 min prior to antigen challenge produced similar concentration-dependent inhibition of allergic histamine release. The IC50s (microM) following 10-min preincubation were as follows: azelastine = 4.8; astemizole = 86.3; ketotifen = 112.2; diphenhydramine = 133 and theophylline = 2040.3. At IC50 level azelastine was about 18, 23, 28 and 425 times as effective as astemizole, ketotifen (newer histamine H1-receptor antagonists), diphenhydramine (a traditional H1-receptor antagonist), and theophylline (a phosphodiesterase inhibitor), respectively. Sodium cromoglycate in a concentration range or 1-1000 microM (0 or 10-min preincubation) failed to exert any inhibitory effect. These data showed that among six drugs tested azelastine is the most potent inhibitor of allergic histamine release from rat peritoneal mast cells.