fluticasone and azelastine

To present a comprehensive, clinically focused scoping review of therapeutic agents and practices comprising the future of allergic rhinitis (AR) management.. A review of the published literature was performed using the PubMed database, published abstracts, and virtual presentations from scientific meetings and posted results on ClinicalTrials.gov.. Primary manuscripts with trial results, case reports, case series, and clinical trial data from ClinicalTrials.gov, PubMed, and articles highlighting expert perspectives on management of AR were selected.. Telemedicine, social media, and mHealth facilitate integrated care for AR management. Pharmacotherapy remains the standard of care for AR management; however, treatment combinations are recommended. Intralymphatic immunotherapy and peptide immunotherapy are the most promising new allergen immunotherapy options. Studies of targeted biologics for AR are ongoing. Probiotics may be beneficial for AR management, particularly Bifidobacterium spp, and as an add-on to allergen immunotherapy.. AR is a chronic and often comorbid condition that requires integrated care for optimal management. New formulations and combinations of existing AR therapies are the most promising and merit future research.

Topics: Allergens; Anti-Allergic Agents; Bifidobacterium; Desensitization, Immunologic; Disease Management; Fluticasone; Humans; Injections, Intralymphatic; Phthalazines; Probiotics; Rhinitis, Allergic

Topics: Administration, Intranasal; Adolescent; Anti-Allergic Agents; Child; Child, Preschool; Drug Combinations; Fluticasone; Humans; Infant; Phthalazines; Rhinitis, Allergic

Combination therapy with intranasal azelastine and fluticasone propionate is an option for treatment of allergic rhinitis. This systematic review and meta-analysis examines existing literature to determine efficacy in treating allergic rhinitis compared to monotherapy.. The PubMed, EMBASE, Cochrane, and MEDLINE databases were systematically searched for randomized controlled trials using AzeFlu nasal spray.. Randomized, controlled trials that reported symptom relief of allergic rhinitis in males and females of all ages were included. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard.. Systematic review identified 8 articles suitable for review. The risk of bias was generally low. All studies exhibited a greater decrease in patient-reported symptom scores in patients treated with combination therapy compared to monotherapy or placebo. Meta-analysis revealed superiority of combination therapy in reducing Total Nasal Symptom Score compared to placebo (mean change from baseline: -2.41; 95% confidence interval [CI], -2.82 to -1.99;. Current evidence supports both efficacy and superiority of combination intranasal azelastine and fluticasone in reducing patient-reported symptom scores in patients with allergic rhinitis. Combination nasal spray should be considered as second-line therapy in patients with allergic rhinitis that is not controlled with monotherapy.

Topics: Administration, Intranasal; Anti-Allergic Agents; Drug Combinations; Fluticasone; Humans; Phthalazines; Randomized Controlled Trials as Topic; Rhinitis, Allergic

Allergic rhinitis is a frequent presenting problem in primary care in the UK, and has increased in prevalence over the last 30 years. When symptomatic, patients report significant reduction in their quality of life and impairment in school and work performance. Achieving adequate symptom control is pivotal to successful allergic rhinitis management, and relies mostly on pharmacotherapy. While it is recognised that most mild-moderate allergic rhinitis symptoms can be managed successfully in primary care, important gaps in general practitioner training in relation to allergic rhinitis have been identified. With the availability of new effective combination therapies, such as the novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (Dymista®; Meda), the majority of allergic rhinitis symptoms can be treated in the primary care setting. The primary objective of this consensus statement is to improve diagnosis and treatment of allergic rhinitis in primary care, and offer guidance on appropriate referral of difficult-to-treat patients into secondary care. The guidance provided herein outlines a sequential treatment pathway for allergic rhinitis in primary care that incorporates a considered approach to improve the management of allergic rhinitis symptoms and improve compliance and patient satisfaction with therapy. Adherence with this care pathway has the potential to limit the cost of providing effective allergic rhinitis management in the UK by avoiding unnecessary treatments and investigations, and avoiding the need for costly referrals to secondary care in the majority of allergic rhinitis cases. The fundamentals presented in this consensus article should apply in most health-care settings.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Algorithms; Anti-Allergic Agents; Drug Combinations; Fluticasone; Histamine Antagonists; Humans; Leukotriene Antagonists; Phthalazines; Rhinitis, Allergic; United Kingdom

The review presents some information on known options for treatment of nonallergic rhinitis (NAR) with introduction to new therapies. The merits and limitations of recent advancements in pharmacotherapy of this common problem are briefly discussed as well.. Intranasal corticosteroids are first-line therapy for NAR. Fluticasone propionate and beclomethasone remain the only topical corticosteroids approved for NAR. The use of azelastine - another first-line option - has also been found to be effective even though NAR is a nonallergic entity by definition. Combination of fluticasone propionate and azelastine is a promising option in achieving better symptom reduction. Coadministration of intranasal corticosteroid and topical decongestants is an attractive topic that requires additional safety studies before recommending treatment. Although promising, no scientifically valid recommendation can be made for treatment of NAR with capsaicin. Surgical options in patients with refractory NAR are limited. New studies demonstrate a lack of correlation between objective outcome of radiofrequency ablation of the inferior turbinate and subjective patient symptoms.. The heterogeneity in clinical presentation makes NAR treatment a daily challenge for otolaryngologists. The diversity of clinical studies with use of unique outcome measures limit systematic reviews which may be instrumental in providing strong recommendations.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Beclomethasone; Capsaicin; Drug Therapy, Combination; Fluticasone; Humans; Nasal Decongestants; Phthalazines; Rhinitis; Sensory System Agents

For any allergic rhinitis (AR) treatment, it is crucial to provide evidence not only of efficacy (assessed in randomized controlled trials (RCTs)) but also of effectiveness in real-life. Observational studies provide valuable data on the use and results associated with interventions prescribed in real-life. However, real-life evidence supporting available AR treatment options is sparse with effectiveness only established for oral antihistamines (desloratadine, ebastine), intranasal corticosteroids (mometasone furoate, fluticasone propionate (FP)), allergen immunotherapy and omalizumab. A novel intranasal formulation of azelastine hydrochloride and FP in a single spray (MP-AzeFlu) shows great promise, with the effectiveness observed in real-life exceeding that noted in RCTs. This review summarises real-life data on MP-AzeFlu, which provides rapid and sustained symptom control irrespective of patient age, AR phenotype or disease severity. We call for high quality real-life research in addition to RCTs to inform future AR treatment guidelines.

Topics: Adrenal Cortex Hormones; Fluticasone; Histamine Antagonists; Humans; Phthalazines; Rhinitis, Allergic

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Benzimidazoles; Butyrophenones; Cyproheptadine; Fluticasone; Histamine H1 Antagonists; Humans; Omalizumab; Phthalazines; Piperidines; Pregnenediones; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

During the last few years, fixed combinations of intranasal antihistamines and corticosteroids have been introduced for treatment of allergic rhinitis. The aim of this systematic review was to assess recent patents and clinical evidence for fixed combinations of intranasal antihistamines and intranasal corticosteroids in allergic rhinitis. Data base searches revealed that intranasal combinations of the antihistamine azelastine with the corticosteroids mometasone furoate, ciclesonide and fluticasone propionate, respectively, have been patented. Four randomized, double-blinded, parallel-group, placebo-controlled, multicenter trials sponsored by the manufacturer evaluated the fixed combination of intranasal azelastine 125 µg and fluticasone propionate 50 µg administered as one dose per nostril b.i.d. in patients with moderate-to-severe symptomatic allergic rhinitis ≥ 12 years of age. Three of the studies were published as a meta-analysis which found the fixed combination of azelastine and fluticasone propionate statistically significantly more efficacious in reducing baseline total nasal symptom score by 5.7 as compared to azelastine (4.4; P < 0.001), fluticasone propionate (5.1; P < 0.001) and placebo (3.0; P < 0.001). The findings were supported by secondary assessments of scores of specific nasal and ocular symptoms. Pharmacokinetic studies have revealed no drug-drug interactions but a discrete increase in bioavailability of fluticasone propionate which was considered clinically unimportant. Further efficacy and quality-of-life studies of combination products of nasal antihistamines and corticosteroids are needed, especially, in primary care settings and in children before fixed combination treatment can be considered first line therapy in allergic rhinitis. Fixed combination treatment of azelastine and fluticasone propionate may offer additional benefit to selected populations of adolescents and adults with moderate-to-severe symptoms.

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Androstadienes; Animals; Drug Combinations; Evidence-Based Medicine; Fluticasone; Histamine Antagonists; Humans; Mometasone Furoate; Patents as Topic; Phthalazines; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Topics: Androstadienes; Animals; Clinical Trials as Topic; Drug Combinations; Fluticasone; Humans; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Chronic Disease; Clenbuterol; Cough; Drug Therapy, Combination; Fluticasone; Histamine H1 Antagonists; Humans; Hypersensitivity, Immediate; Phthalazines; Prednisolone

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

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

The safety of a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) has been established in adults and adolescents with allergic rhinitis but not in children <12 years old.. To evaluate the safety and tolerability of an intranasal formulation of AZE and FP in children ages 4-11 years with allergic rhinitis.. The study was a randomized, 3-month, parallel-group, open-label design. Qualified patients were randomized in a 3:1 ratio to AZE/FP (n = 304) or fluticasone propionate (FP) (n = 101), one spray per nostril twice daily, and to one of three age groups: ≥4 to <6 years, ≥6 to <9 years, and ≥9 to <12 years. Safety was assessed by child- or caregiver-reported adverse events, nasal examinations, vital signs, and laboratory assessments.. The incidence of treatment-related adverse events (TRAEs) was low in both the AZE/FP (16%) and FP-only (12%) groups after 90 days' continuous use. Epistaxis was the most frequently reported TRAE in both groups (AZE/FP, 9%; FP, 9%), followed by headache (AZE/FP, 3%; FP, 1%). All other TRAEs in the AZE/FP group were reported by ≤1% of the children. The majority of TRAEs were of mild intensity and resolved spontaneously. Results of nasal examinations showed an improvement over time in both groups, with no cases of mucosal ulceration or nasal septal perforation. There were no unusual or unexpected changes in laboratory parameters or vital signs.. The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered on ClinicalTrials.gov (NCT01794741).

Topics: Administration, Intranasal; Anti-Allergic Agents; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Fluticasone; Humans; Incidence; Male; Nasal Sprays; Phthalazines; Rhinitis, Allergic; Treatment Outcome; United States

Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers.. To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14°C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu (n = 20) or placebo (n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post-CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post-CDA challenge at each visit.. The minimum cross-sectional area (p < 0.05), cough count (p < 0.05), and substance P (p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment.. This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly.

Topics: Adult; Air; Anti-Inflammatory Agents; Bronchial Provocation Tests; Cold Temperature; Cough; Female; Fluticasone; Humans; Male; MicroRNAs; Middle Aged; Nasal Mucosa; Phthalazines; Pilot Projects; Rhinitis, Vasomotor

This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials.. A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups.. A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms.. MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Topics: Caregivers; Child; Child, Preschool; Disease Progression; Drug Combinations; Female; Fluticasone; Humans; Male; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Surveys and Questionnaires; Symptom Assessment

It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses.. 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses.. MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom.. MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Cedrus; Disease Progression; Drug Combinations; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome; Young Adult

• The topical second generation anti-histamine azelastine hydrochloride (AZE) and the potent corticosteroid fluticasone propionate (FP) are well established first-line treatments in allergic rhinitis (AR). • MP29-02, a novel intranasal AZE and FP formulation, has been shown to control AR symptoms faster and better than standard intranasal AZE or FP. • The systemic bioavailabilities of marketed AZE and FP nasal spray products have been established at about 40% and 1% only, respectively. • For new combination medicinal products such as MP29-02, the determination of possible pharmacokinetic (PK) drug-drug interactions between both active components and formulation-based bioavailability alterations is essential.. • This paper provides for the first time information on potential drug-drug interactions, AZE and FP bioavailability and disposition characteristics of each component administered by the novel nasal spray formulation MP29-02. • The studies employed highly sensitive FP and AZE LC-MS/MS assays and could therefore be conducted with recommended therapeutic doses, thereby circumventing previously recognized draw-backs that required nasal bioavailability studies to be conducted using supra-therapeutic doses. • No significant PK drug-drug interaction between the active components AZE and FP was noted for MP29-02. • AZE bioavailabilty was equivalent when MP29-02 data were compared with MP29-02-AZE-mono and Astelin®. • Increased FP exposure was observed with MP29-02-based products compared with FP-BI. FP serum concentrations were generally very low with all investigational products suggesting no clinically meaningful pharmacodynamic differences in terms of systemic safety.. To determine azelastine hydrochloride (AZE) and fluticasone propionate (FP) bioavailabilities of the novel nasal spray combination product MP 29-02, compared with MP29-02-based products containing only AZE (MP29-02-AZE-mono), FP (MP29-02-FP-mono), marketed AZE and FP single entity products (Astelin® and FP Boehringer-Ingelheim; FP-BI).. Two randomized, three period, six sequence, three treatment crossover studies were conducted in healthy subjects. Study 1 administered 200 µg FP as MP29-02, MP29-02-FP-mono or FP-BI. Study 2 administered 548 µg AZE as MP29-02, MP29-02-AZE-mono or Astelin®. Each dose consisted of two sprays/nostril. Serum FP and plasma AZE were followed over 24 (FP) and 120 h (AZE) and quantified by LC-MS/MS. Peak (C(max) ) and total exposures AUC(0,t(last) ) were compared between the treatments by anova.. Study 1: Average FP C(max) was very low with all products (≤ 10 pg ml(-1) ). FP AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-FP-mono and MP29-02 : FP-BI ratios (%) were 93.6 (83.6, 104.7) and 161.1 (137.1, 189.3). Corresponding ratios for C(max) were 91.0 (82.5, 100.4) and 157.4 (132.5, 187.1). Study 2: AZE AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-AZE-mono and MP29-02 : Astelin® ratios (%) were 98.8 (91.0, 107.4) and 105.5 (95.6, 116.4). Corresponding outcomes for C(max) were 102.7 (92.1, 114.4) and 107.3 (92.6, 124.3).. No interactions of AZE and FP were found with the MP29-02 formulation. Azelastine bioavailability was similar for MP29-02 and Astelin®. Maximum and total FP exposure was higher for MP29-02-based products compared with FP-BI. FP concentrations were generally very low with all investigational products and did not suggest clinically meaningful differences concerning systemic safety.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Biological Availability; Chromatography, High Pressure Liquid; Drug Combinations; Drug Delivery Systems; Drug Interactions; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal; Tandem Mass Spectrometry; Young Adult

Moderate-to-severe allergic rhinitis (AR) is a challenge to treat, with many patients using multiple therapies and achieving limited symptom control. More effective therapies must be developed and tested in well-controlled, randomized, prospective studies with a direct comparison to current standards.. The aim of these studies was to investigate the efficacy of MP29-02 (a novel formulation of azelastine and fluticasone propionate [FP]) in patients with moderate-to-severe seasonal allergic rhinitis (SAR) and to compare its efficacy with 2 first-line therapies (ie, intranasal azelastine and intranasal FP) in this population.. Three thousand three hundred ninety-eight patients (≥12 years old) with moderate-to-severe SAR were enrolled into 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group trials (MP4002 [NCT00651118], MP4004 [NCT00740792], and MP4006 [NCT00883168]). Each trial was conducted for 14 days during different allergy seasons. The primary efficacy variable was the sum of the morning and evening change from baseline in reflective total nasal symptom score (range, 0-24) over the treatment period. Outcomes for the meta-analysis included efficacy according to disease severity and time to response in relevant responder criteria.. In the meta-analysis MP29-02 reduced the mean reflective total nasal symptom score from baseline (-5.7 [SD, 5.3]) more than FP (-5.1 [SD, 4.9], P < .001), azelastine (-4.4 [SD, 4.8], P < .001), or placebo (-3.0 [SD, 4.2], P < .001). This benefit was observed from the first day of assessment, with improvement in each individual nasal symptom, even in the patients with the most severe disease. MP29-02 achieved response consistently days earlier and showed greater efficacy in patients with moderate-to-severe rhinitis than FP and azelastine.. MP29-02 represents a novel therapy that demonstrated superiority to 2 first-line therapies for AR. Patients with moderate-to-severe SAR achieved better control, and their symptoms were controlled earlier with MP29-02 than with recommended medications according to guidelines.

Topics: Administration, Intranasal; Adult; Androstadienes; Disease Progression; Drug Combinations; Female; Fluticasone; Guidelines as Topic; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Seasons; Severity of Illness Index; Young Adult

A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone.. To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray.. This 14-day, multicenter, randomized, double-blind study was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in, 610 patients with moderate-to-severe nasal symptoms were randomized to treatment with (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All treatments were given as 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing.. All 3 active groups were statistically superior (P

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Aged; Allergens; Androstadienes; Cedrus; Child; Double-Blind Method; Drug Combinations; Drug Synergism; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Pollen; Rhinitis, Allergic, Seasonal

To our knowledge, there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid, although anecdotal reports of the use of these agents in combination are common.. To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone.. This randomized, 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms were randomized to treatment with the following: (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion.. All 3 groups had statistically significant (P < .001) improvements from their baseline TNSS after 2 weeks of treatment. The TNSS improved 27.1% with fluticasone nasal spray, 24.8% with azelastine nasal spray, and 37.9% with the 2 agents in combination (P < .05 vs either agent alone). All 3 treatments were well tolerated.. The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Headache; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic, Seasonal; Taste; Treatment Outcome

Acoustic rhinometry (AR) was used for objective measurements of nasal cavity dimensions in conjunction with a 100-mm horizontal visual analogue scale (VAS) for simultaneous subjective assessments of nasal sensations of airflow. Studies were conducted on 45 patients with perennial allergic rhinitis before, during and after a 2-week period of treatment with oral emedastine difumarate, azelastine hydrochloride, and xiao qing long tang (a homeopathic decongestant), as well as intranasal fluticasone propionate aqueous nasal spray. During the treatment period, there was a significant increase in the right and left minimum cross-sectional areas (MCA) of the nose and/or nasal cavity volumes (NCV) in all groups. The average increase in MCA ranged from 21-39% after 1 week of treatment and 16-39% after 2 weeks, whereas that in the NCV ranged from 16-24% and 19-24%, respectively. Post-treatment measurements were not significantly different from the corresponding pre-treatment ones. These findings were in close agreement with that obtained with VAS, demonstrating that AR can be used to validate the application of VAS in the evaluation of nasal airflow during medical therapy.

Topics: Acoustics; Administration, Intranasal; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Benzimidazoles; Evaluation Studies as Topic; Female; Fluticasone; Follow-Up Studies; Histamine H1 Antagonists; Homeopathy; Humans; Imidazoles; Male; Middle Aged; Naphazoline; Nasal Cavity; Nasal Decongestants; Nasal Obstruction; Nose; Phthalazines; Pulmonary Ventilation; Reproducibility of Results; Rhinitis, Allergic, Perennial

Eustachian tube dysfunction (ETD) is frequent in children with adenoid hypertrophy (AH). Although the most common treatment of AH is surgical removal of adenoid tissue, numerous studies have reported the efficacy of intranasal steroids. The effects of the intranasal steroid and azelastine combination on AH and ETD have not been reported before. In this study, we tried to determine the effects of 3-month intranasal Azelastine-Fluticasone dipropionate combination (Aze-Flu) treatment in children with ETD and AH.. 100 children who had open mouth sleep, snoring, and sleep apnea and were diagnosed with AH and ETD participated in this study. The mean age was 7.73 ± 2.37 (4-14 years). The rates of adenoid tissue hypertrophy and choanal occlusion were evaluated using a rigid pediatric nasal endoscope and reassessed after 3 months of Aze-Flu nasal spray treatment. The function of the Eustachian tube (ET) was evaluated before and after medical treatment using the Eustachian tube score, the Eustachian dysfunction test-7 (ETS-7) and tubomanometry (TMM).. The results were evaluated in 100 patients with AH and ETD. The adenoid tissue to choana rate was 82% before treatment and decreased to 37% after treatment. The ETS-7 test score was 6.36 before treatment and increased to 9.72 at the end of 3 months. Both the regression of the adenoid tissue and the improvement in the Eustachian function scores were statistically significant (p < 0.05).. AH significantly increases the frequency of ETD. In this study, it was observed that Aze-Flu treatment was significantly effective in both regression of the adenoid tissue and Eustachian tube dysfunction. We believe that it can be applied as an initial therapy in children with AH and associated ETD.

Topics: Adenoids; Child; Child, Preschool; Ear Diseases; Eustachian Tube; Fluticasone; Humans; Hypertrophy; Middle Ear Ventilation

Azelastine HCl (AZ) and fluticasone propionate (FL) nasal spray drug product is commonly used in the treatment of allergic rhinitis worldwide. To date, the impurity profiling of this product has not been reported.. The present study aimed to develop and validate a novel RP-HPLC stability-indicating analytical method for the estimation of impurities from AZ and FL nasal spray drug product.. A mixture of octane sulfonic acid sodium salt and trifluroacetic acid is used as a mobile phase A. Acetonitrile is used as a mobile phase B. Good separation was achieved on Baker bond phenyl hexyl, 250 × 4.6, 5 µm column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 239 nm.. The LOD and LOQ were found to be 0.006 and 0.019 µg/mL for AZ and 0.010 and 0.030 µg/mL for FL, respectively. The correlation coefficient for all the known impurities and principal analytes was 0.999 from LOQ level to 150% of standard concentration. The recovery for all the known impurities was found to be between 90 and 110%. In the stress study, 15% degradation was observed in basic conditions and 8.7% in acidic conditions. No significant degradation was observed in thermal and oxidative conditions.. An impurity profiling method for AZ and FL combination nasal spray product was successfully developed, validated, and demonstrated to be accurate, precise, specific, robust, and stability-indicating. The method can be routinely used for impurity testing of commercial batches in QC laboratories in the pharmaceutical industry.. No impurity study has been reported for this combination product until now.

Topics: Chromatography, High Pressure Liquid; Fluticasone; Nasal Sprays; Phthalazines

Topics: Fluticasone; Humans; Otolaryngology; Phthalazines; Rhinitis, Allergic

The combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.. Moderate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self-reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples.. In nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (-2.57 to -0.45 Log2 fold change [FC]), 24 genes upregulated (0.49-1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (-1.53 to -0.58 Log2 FC), six genes upregulated (1.07-1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (-1.68 Log2 FC), four genes upregulated (0.59-1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment.. AZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression.

Topics: Fluticasone; Gene Expression; Humans; Phthalazines; Rhinitis, Allergic, Seasonal

Topics: Androstadienes; Anti-Inflammatory Agents; Drug Combinations; Fluticasone; Gene Expression; Humans; Mucous Membrane; Phthalazines

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Allergic Agents; Child; Child, Preschool; Drug Combinations; Fluticasone; Histamine H1 Antagonists, Non-Sedating; Humans; Nasal Sprays; Phthalazines; Rhinitis, Allergic

Phenotyping allergic rhinitis (AR) by immunoglobulin E (IgE) sensitivity and comorbidities may help characterize AR and provide a framework for treatment decisions.. This prospective, noninterventional study evaluated the effectiveness of MP-AzeFlu (azelastine hydrochloride plus fluticasone propionate intranasal spray formulation) across AR phenotypes. Patients with moderate-to--severe seasonal or perennial AR for whom MP-AzeFlu was prescribed were enrolled. AR subpopulations (ARPs) were assigned based on the classification of IgE response and comorbidities. AR symptoms over the previous 24 h were documented using an AR visual analog scale (AR-VAS), with ratings from "not at all bothersome" (0 mm) to "extremely bothersome" (100 mm), at the inclusion visit and on days 1, 3, 7, and the last day of the study (approximately day 14). AR quality-of-life measures were recorded using a VAS.. A total of 1,103 patients with AR were included. Mean baseline AR-VAS scores ranged from 70.3 to 75.1 mm (severe) across ARPs. In the overall population, 86.6% of patients responded to treatment (AR-VAS score <50 mm on ≥1 days). In the ARPs, response rates ranged from 79.3 to 89.6%. Mean reduction in AR-VAS scores ranged from 47.9 to 40.9 mm, a decrease from severe to mild across all ARPs. Quality-of-life VAS scores were similarly reduced in the total population and ARPs.. MP-AzeFlu treatment reduced VAS severity and quality-of-life scores from baseline in the total population and ARPs, supporting MP-AzeFlu as an effective treatment for all patients with moderate-to-severe AR, regardless of AR phenotype or comorbidities.

Topics: Administration, Intranasal; Adult; Comorbidity; Drug Combinations; Female; Fluticasone; Humans; Immunoglobulin E; Male; Middle Aged; Nasal Sprays; Phenotype; Phthalazines; Prospective Studies; Quality of Life; Rhinitis, Allergic; Severity of Illness Index; Treatment Outcome; Visual Analog Scale; Young Adult

Allergic rhinitis (AR) control is a priority in the European Union (EU), and Allergic Rhinitis and its Impact on Asthma (ARIA) has endorsed a visual analogue scale (VAS) as the new language of AR control. This study evaluated the effectiveness of MP-AzeFlu (Dymista®, antihistamine [azelastine], and intranasal corticosteroid [fluticasone propionate]) using a VAS in real-life clinical practice in Denmark.. The multicenter, prospective, non-interventional study included 170 patients (≥12 years) with ARIA-defined moderate-to-severe AR prescribed MP-AzeFlu. Patients assessed symptom severity using a VAS (0 to 100 mm) on days 0, 1, 3, and 7 and after ∼14 days of MP-AzeFlu use. On day 3, patients assessed their disease as well controlled, partly controlled, or uncontrolled. Proportions of patients achieving VAS score cutoffs (well-controlled, partly controlled) were also calculated.. MP-AzeFlu reduced mean ± standard deviation VAS score from 67.1 ± 19.3 mm at baseline to 28.4 ± 23.7 mm on the last day, a reduction of 38.8 ± 27.3 mm. At day 3, 85.6% of patients considered their symptoms to be partly or well controlled. Effectiveness was consistent across disease severity, phenotype (seasonal, perennial, or combined AR), and patient age. Respectively, 28.2%, 44.2%, 61.6%, and 71.4% of patients achieved ≤38 mm well-controlled VAS score cutoff on days 1, 3, and 7, and the last day.. MP-AzeFlu provided effective, rapid, and sustained symptom control in a real-life setting among patients from Denmark. These results align with EU and ARIA objectives and support the effectiveness of MP-AzeFlu for the treatment of AR in real life.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Denmark; Drug Combinations; Female; Fluticasone; Histamine Antagonists; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic; Treatment Outcome; Young Adult

The European Union has prioritised allergic rhinitis (AR) control. A visual analogue scale (VAS) has been endorsed as the AR control language and embedded into the most recent MACVIA-ARIA guideline. This study assessed the effectiveness and safety of MP-AzeFlu using a VAS in a real-life study in Sweden.. 431 patients aged 12 years or over with ARIA-defined moderate to severe AR were included in this multicentre, prospective, non-interventional study and prescribed MP-AzeFlu. Patients assessed symptom severity using a VAS from 0 (not at all bothersome) to 100 mm (very bothersome) on Days 0, 1, 3 and 7, and after approximately 14 days in the morning before using MP-AzeFlu. Patients' perceived level of disease control was assessed on Day 3. The proportion of patients who achieved a defined VAS score cutoff for well- and partly controlled AR was also calculated.. MP-AzeFlu reduced mean (SD) VAS score from 67.9 (16.1) mm at baseline to 32.1 (22.8) mm on the last day. Results were consistent irrespective of severity, phenotype, patient age class or previous treatment. By Day 3, 84.0% of patients reported well- or partly controlled symptoms. Overall, 17.7%, 32.2%, 53.8% and 64.2% of patients achieved a 38 mm or greater "well-controlled" VAS score cutoff on Day 1, 3 and 7 and last day, respectively.. MP-AzeFlu provided rapid, effective and sustained symptom control in patients with AR from Sweden in a realworld setting, aligning with EU and MACVIA-ARIA initiatives and supporting the effectiveness of MP-AzeFlu for AR treatment in real life.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Child; Cohort Studies; Fluticasone; Humans; Phthalazines; Prospective Studies; Rhinitis, Allergic; Sweden; Treatment Outcome; Visual Analog Scale; Young Adult

Allergic Rhinitis and its Impact on Asthma (ARIA) and the European Union (EU) recommend a shift to guide allergic rhinitis (AR) treatment decisions from symptom severity to disease control, using a simple visual analogue scale (VAS). Using this VAS we assessed, in a real-life study in Romania, the effectiveness of MP-AzeFlu nasal spray.. In this multi-centre, prospective, non-interventional study, 253 patients (over 11 years old) with moderate-to-severe AR were prescribed MP-AzeFlu and assessed their symptoms on a VAS (0 (not at all bothersome) to 100 mm (very bothersome)) on Days 0, 1, 3, 7 and 14. The proportion of patients who achieved a defined VAS score cut-off for well-controlled (38 mm) AR were also calculated. Patients perception of disease control was assessed on Day 3.. MP-AzeFlu use was associated with a mean (standard deviation) VAS score reduction from 78.4 (15.1) mm at baseline to 14.7 (15.1) mm on the last day. Effectiveness was consistent irrespective of disease severity, phenotype or patient age. 83.4% of patients achieved the smaller than 39 mm well-controlled VAS score cut-off by last day and 95.2% considered their symptoms to be well- or partly controlled at Day 3.. MP-AzeFlu provided rapid, effective and sustained AR symptom control in a real-life setting in Romania, irrespective of severity, phenotype or patient age, aligning with ARIA and EU recommendations and supporting the position of MP-AzeFlu as the drug of choice for the treatment of moderate-to-severe AR.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Child; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Phthalazines; Prospective Studies; Rhinitis, Allergic; Romania; Treatment Outcome

MP 29-02, which contains fluticasone propionate and azelastine hydrochloride, is used as a topical nasal application for the treatment of seasonal and perennial allergic rhinitis. Although a multitude of data is available on the clinical symptom reduction and treatment safety of MP 29-02, the effect of MP 29-02 on ciliary beat frequency (CBF) has not been evaluated thus far.. MP 29-02-containing solution was applied at concentrations of 2.5, 5, 10, and 20% to 14 healthy subjects, and nasal ciliated epithelial cells were then visualized using a phase-contrast microscope. CBF was measured after the application of MP 29-02. For a comparison, fluticasone propionate was used. CBF measurements were then performed for 15 min at 22 °C. Ringer's solution was applied as a negative control.. MP 29-02 significantly reduced CBF at all the tested concentrations compared with that of the control group within the observation time. At a 2.5% concentration, MP 29-02 significantly reduced CBF from 6.81 Hz (SD ± 1.35 Hz) at baseline to 4.88 Hz (SD ± 1.52 Hz, p < 0.001) after 15 min. In contrast, for fluticasone propionate, a significant reduction was observed only with the 20% concentration after 5, 10, and 15 min.. MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.

Topics: Administration, Intranasal; Adult; Androstadienes; Drug Combinations; Epithelial Cells; Female; Fluticasone; Humans; In Vitro Techniques; Male; Middle Aged; Nasal Mucosa; Phthalazines; Rhinitis, Allergic, Perennial

Objectives To examine the association of industry payments for brand-name intranasal corticosteroids with prescribing patterns. Study Design Cross-sectional retrospective analysis. Setting Nationwide. Subjects and Methods We identified physicians prescribing intranasal corticosteroids to Medicare beneficiaries 2014-2015 and physicians receiving payment for the brand-name intranasal corticosteroids Dymista and Nasonex. Prescription and payment data were linked by physician, and we compared the proportion of prescriptions written for brand-name intranasal corticosteroids in industry-compensated vs non-industry-compensated physicians. We associated the number and dollar amount of industry payments with the relative frequency of brand-name prescriptions. Results In total, 164,587 physicians prescribing intranasal corticosteroids were identified, including 7937 (5%) otolaryngologists; 10,800 and 3886 physicians received industry compensation for Dymista and Nasonex, respectively. Physicians receiving industry payment for Dymista prescribed more Dymista as a proportion of total intranasal corticosteroid prescriptions than noncompensated physicians (3.1% [SD = 9.6%] vs 0.2% [SD = 2.5%], respectively, P < .001). Similar trends were seen for Nasonex (12.0% [SD = 16.8%] vs 4.8% [SD = 13.6%], P < .001). The number and dollar amount of payment were significantly correlated to the relative frequency of Dymista (ρ = 0.26, P < .001 and ρ = 0.20, P < .001, respectively) and Nasonex prescriptions (ρ = 0.09, P < .001 and ρ = 0.15, P < .001, respectively). For Dymista, this association was stronger in otolaryngologists than general practitioners ( P < .001). There was a stronger correlation between the percentage of prescriptions and the number and dollar amount of payments for Dymista than for Nasonex ( P = .014 and P < .001). Conclusions Industry compensation for brand-name intranasal corticosteroids is significantly associated with prescribing patterns. The magnitude of association may depend on physician specialty and the drug's time on the market.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Conflict of Interest; Cross-Sectional Studies; Drug Combinations; Drug Industry; Drug Utilization; Female; Fluticasone; Gift Giving; Humans; Interinstitutional Relations; Male; Mometasone Furoate; Phthalazines; Practice Patterns, Physicians'; Prescription Drugs; Retrospective Studies

Nasal cavity breakthrough to the airways of the lungs is associated with nasally inhaled droplets whose size is smaller than ca. 10 μm aerodynamic diameter that behave as an aerosol rather than a spray in terms of their transport. The purpose of the present laboratory-based study was to evaluate a nasal product quality control procedure involving a new inlet for the quantification of mass of such droplets emitted by commercially available aqueous nasal spray pump products by cascade impactor. This inlet is more representative of the adult nasal vestibule in terms of entry angle for the spray as well as internal volume for plume expansion. Sampling was also undertaken via a spherical 1-L glass expansion vessel as inlet, previously established for quantification of these aerosol droplets. The selected solution- and suspension-formulated products containing azelastine and fluticasone propionate respectively were shown to contain < 1% of the total spray mass per actuation associated with droplets < 14.1 μm aerodynamic diameter. These measurements were consistent with laser diffraction-based measurements of the entire droplet size distribution. Comparable measures of aerosol droplet mass fraction were obtained when the spray was sampled by the cascade impactor method using either the 1-L glass expansion chamber or the new metal inlet as entry for the spray produced by either product evaluated. We conclude that the metal inlet has the potential to be adopted as a suitable induction port in the assessment of nasal product quality, where currently no standardized inlet exists.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Aerosols; Fluticasone; Humans; Nasopharynx; Nebulizers and Vaporizers; Phthalazines

Most allergic rhinitis (AR) patients have moderate-to-severe, persistent disease. Meda Pharma's AzeFlu (MP-AzeFlu) combines intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation in a single device to treat AR. This prospective, noninterventional study sought to assess the effectiveness of MP-AzeFlu (one spray/nostril twice daily; 548 µg AZE/200 µg FP daily dose) in relieving AR symptom severity.. A visual analogue scale (VAS) was used prior to MP-AzeFlu treatment on days 0, 1, 3, 7, 14, 21, 28, 35, and 42 by 53 persistent AR (PER) patients seen in routine clinical practice in Ireland. An endoscopy was performed on days 0 and 28, and symptoms of edema, discharge, and redness were scored on a three-point scale (for both nostrils).. Patients using MP-AzeFlu experienced rapid VAS score reduction from 73.4 mm (standard deviation [SD], 20.3) at Day 0 to 31.5 mm (SD, 25.0) at day 28 (P < 0.0001) to 28.1 mm (SD, 24.1) at day 42 (P < 0.0001), a 45.3-mm reduction. On average, patients achieved a clinically relevant VAS score cutoff of 50 mm before Day 7. Total endoscopy score decreased from 7.5 mm (SD, 3.1) at baseline to 3.5 mm (SD, 2.5) at Day 28. The incidence of severe edema on endoscopy decreased from 53.1% at baseline to 3.8% at Day 28. A similar reduction in the incidence of thick/mucousy discharge (from 28.3% to 4.8%) and severe redness (from 34.9% to 0%) was also observed.. MP-AzeFlu provided effective, rapid control of PER as assessed by VAS in a real-world clinical setting in Ireland. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved mucosal appearance after 28 days. These results confirm the safety of MP-AzeFlu and exceed the efficacy demonstrated in phase 3 clinical studies for controlling AR in PER patients.

Topics: Adolescent; Adult; Aged; Child; Edema; Endoscopy; Female; Fluticasone; Humans; Ireland; Male; Middle Aged; Nasal Mucosa; Nasal Sprays; Phthalazines; Prospective Studies; Rhinitis, Allergic; Treatment Outcome; Visual Analog Scale; Young Adult

The aims of this study were (1) to characterise the type of patient prescribed MP-AzeFlu (Dymista, a novel formulation of azelastine hydrochloride, fluticasone propionate and excipients in a single spray) in real life in the UK and physicians' reasons for prescribing it and (2) to quantify the personal and societal burden of allergic rhinitis (AR) in the UK prior to MP-AzeFlu prescription.. This multicentre, non-interventional study enrolled patients (n=193) with moderate-to-severe AR and acute symptoms who were eligible to receive treatment with MP-AzeFlu according to its licensed indications. Information was gathered on patient demographics, AR history and symptom severity, symptomatology and AR treatments in the previous calendar year (prior to MP-AzeFlu prescription). Physicians also recorded the number of previous AR visits, specific reasons for these visits and their reason for prescribing MP-AzeFlu.. Most patients had seasonal AR either alone (10.4%) or in combination with perennial AR (35.2%), but many had AR of unknown origin (35.8%). Prior to MP-AzeFlu prescription, patients reported troublesome symptoms (78.2%) and sleep disturbance (64.8%), with congestion considered the most bothersome (54.4%) and ocular symptoms reported by 68.4% of patients. The most frequent reason for MP-AzeFlu prescription was that other therapies were not sufficient in the past (78.8%) or not sufficient to treat acute symptoms (16.1%). 79.3% of patients reported using ≥2 AR therapies in the past year. An average of 1.6 (SD 1.9) doctor visits due to AR were reported prior to MP-AzeFlu prescription.. In the UK, MP-AzeFlu was prescribed for individuals (≥12 years) with moderate/severe AR irrespective of (1) previous AR treatment (mono or multiple), (2) previous or likely treatment failure, (3) phenotype, (4) number of previous physician visits for AR and (5) for the relief of both acute symptoms and in anticipation of allergen exposure

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Child; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic; United Kingdom; Young Adult

The purpose of this study was to investigate the effect of MP-AzeFlu on olfaction and the interaction between severity of allergic rhinitis and olfactory improvement after therapy.. A prospective, multicenter, observational study was performed on 47 patients with persistent allergic rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and the proof of allergen sensitization from positive skin-prick tests, specific immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory function was assessed at baseline and at 1 and 3 months of therapy using the "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a visual analog scale (VAS) at each given time-point.. MP-AzeFlu was found to be associated with a significant improvement in TDI score, from 23.7 at baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of treatment. Furthermore, a highly significant improvement of symptoms over time (p < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be demonstrated. Most importantly, there was a highly significant interaction between the severity of allergic rhinitis and olfactory function (p < 0.001) and VAS (p < 0.001).. MP-AzeFlu is associated with olfactory improvement in persistent allergic rhinitis patients. Further, the modified ARIA severity classification is an indicator of patients' olfactory function. Moreover, assessment of olfaction seems to be a reliable indicator of the clinical success of antiallergic/antiinflammatory therapy.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Female; Fluticasone; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic, Perennial; Smell; Treatment Outcome; Young Adult

Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p=0.05.

Topics: Dosage Forms; Fluticasone; Phenylethyl Alcohol; Phthalazines; Reference Standards; Reproducibility of Results; Spectrophotometry

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Fluticasone; Humans; Phthalazines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Allergic rhinitis affects over 20% of the UK population. It can have a significant impact on quality of life and interferes with both attendance and performance at school and at work.1 Intranasal corticosteroids are widely recognised as the most effective symptomatic treatment available, but oral or intranasal new generation antihistamines are usually offered as first-line treatment for intermittent symptoms.1,2 Patients with moderate to severe allergic rhinitis may require a combination of drugs, and many patients only achieve limited control of their symptoms.3 Dymista is described as a novel intranasal formulation combining the antihistamine azelastine hydrochloride with the corticosteroid fluticasone propionate.3 It is licensed for the relief of symptoms of moderate to severe seasonal and perennial allergic rhinitis in adults and adolescents if monotherapy with either intranasal antihistamine or glucocorticoid is not considered sufficient.4 The manufacturer claims that compared with fluticasone or azelastine alone, Dymista is twice as effective (when placebo effect is excluded) in providing relief from both nasal and ocular symptoms, and leads to greater overall relief from nasal symptoms. It also claims that Dymista controls nasal symptoms up to 6 days faster than fluticasone.5 Here we consider the evidence for Dymista and whether it represents a significant advantage in the management of patients with allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Drug Combinations; Fluticasone; Humans; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Time Factors

Allergic rhinitis is a very common disease that causes high economic costs. Furthermore inadequate treatment can lead to bronchial asthma. Against this background, drugs for the treatment of allergic rhinitis should be evaluated from a comprehensive medical-economic perspective. The new combination of an antihistamine and a corticosteroid, introduced in the market in 2013, emerges as useful pharmaceutical alternative, both with regard to the medical outcome parameters as well as cost-effectiveness.

Topics: Absenteeism; Administration, Intranasal; Adolescent; Adult; Androstadienes; Asthma; Child; Child, Preschool; Cost-Benefit Analysis; Drug Combinations; Female; Fluticasone; Germany; Humans; Male; National Health Programs; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Socioeconomic Factors

For locally acting drugs, an extended residence time in the nasal cavity is desirable and related to a prolonged effect. We sought to develop a model for comparative determination of intranasal pharmacokinetics. We embedded human respiratory tissue into a solid matrix and coated the surface with artificial nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were applied onto the surface and removed after 30 min to simulate mucociliary clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. FP and Bud were initially bound to the same extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP or Bud. After equilibrium with plasma, approximately 5-fold higher tissue concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud were determined. This tissue retention revealed an excellent correlation with the volume of distribution of the respective drugs (r=0.9999, p ≤ 0.05). The inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced compared to AZ. The present model realistically mirrors conditions in vivo where solubility and tissue absorption of intranasally applied drugs compete with mucociliary clearance mechanisms.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Administration, Intranasal; Aerosols; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Budesonide; Cell Line, Tumor; Delayed-Action Preparations; Epithelial Cells; Fluticasone; Glucocorticoids; Histamine Antagonists; Humans; Interleukin-8; Lung; Lung Neoplasms; Mucociliary Clearance; Nasal Lavage Fluid; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal

The postnasal drip (PND) syndrome is often linked as a cause of chronic cough although this is disputed.. We examined the effect of specific topical treatment of rhinosinusitis on cough in patients presenting with a chronic cough associated with a postnasal drip or 'nasal catarrh'.. Patients presenting with a chronic cough and who complained of PND were enrolled and symptoms of PND and cough were assessed by questionnaire and by a capsaicin cough response. Rhinosinusitis was assessed by questionnaires, direct examination of the nose and by high-resolution computed tomography. In an open study, they were treated with fluticasone nasules, ipratropium bromide and azelastine nasal sprays for 28 days, after which they were re-assessed.. Eighteen out of 21 patients completed the study. All patients reported having the presence of mucus in the throat. Mean cough score improved post-treatment (p<0.05), but there was no significant change in capsaicin cough sensitivity or nasal catarrh questionnaire score. There was improvement in anterior nasal discharge symptom scores (p=0.005) and in endoscopic nasal scores post-treatment (p<0.01), with a tendency to improved PND scores.. In a pilot open 'real-life' study treatment targeted towards rhinosinusitis accompanying PND syndrome and chronic cough led to an improvement in cough. A randomised controlled study is now needed to confirm or refute these findings.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Cough; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Mucosa; Phthalazines; Quality of Life; Rhinitis; Sinusitis; Surveys and Questionnaires; Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

Topics: Androstadienes; Anti-Allergic Agents; Drug Therapy, Combination; Fluticasone; Humans; Phthalazines; Rhinitis, Allergic, Seasonal

A normal ciliary beat frequency of ciliated cells is necessary for the mucociliary clearance of the nose and paranasal sinuses. An in vitro investigation was performed to evaluate the influence of topical corticosteroids and antihistamines on the ciliary beat frequency of human nasal mucosa. The nasal sprays examined contained the corticosteroids budesonide or fluticasone propionate and the topical antihistamines azelastine or levocabastine. All tests were performed on cell cultures of human nasal mucosa during constant conditions. Three of the four nasal sprays tested contained benzalkonium chloride as preservative. An irreversible cessation of ciliary movement was observed in all cells exposed to nasal sprays containing benzalkonium chloride in a 50 per cent solution. The nasal spray containing budesonide was benzalkonium chloride-free and caused minor but fully reversible decreases in ciliary beat frequency after 20 min. As benzalkonium chloride can cause complete standstill of ciliary beat frequency in vitro in human nasal mucosa, we recommend that this preservative should not be used anymore in topical nasal medications.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Benzalkonium Compounds; Budesonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; In Vitro Techniques; Mucociliary Clearance; Nasal Mucosa; Phthalazines; Piperidines; Preservatives, Pharmaceutical