MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial.

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.

Treatment with azelastine hydrochloride and fluticasone propionate in a single delivery device of young children and adolescents with allergic rhinitis.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

A review of the efficacy and safety of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with asthma.

BACKGROUND: Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. OBJECTIVE: An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. METHODS: A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. RESULTS: Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. CONCLUSION: Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Diagnosis and management of allergic conjunctivitis in pediatric patients.

BACKGROUND: Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. OBJECTIVE: To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. METHODS: To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. RESULTS: A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. CONCLUSION: The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis.

BACKGROUND: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children. OBJECTIVE: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup in a randomized double-blind study of children, ages 6-11 years, with SAR. METHODS: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n = 231) for 2 weeks. The primary efficacy end point was change from baseline in the subject's mean reflective total symptom severity complex (TSSC) score over 14 days. RESULTS: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated with placebo over 14 days (least square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score improvement over 14 days between the cetirizine versus loratadine groups (-2.1 versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8 versus -1.6; p = 0.230) were not statistically significant. Predominant adverse events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects. CONCLUSION: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR symptoms in children ages 6-11 years. Symptom improvement was not significantly different between the loratadine 10 mg and placebo groups.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in children with perennial allergic rhinitis.

BACKGROUND: Beclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol at 80 µg/day in children with PAR. METHODS: This 12-week, phase 3, double-blinded, placebo-controlled, parallel-group study randomized 547 children (4-11 years old) with PAR to once-daily BDP nasal aerosol at 80 µg/day or placebo. The primary end point was change from baseline in average morning and evening reflective total nasal symptom score (rTNSS) during the first 6 weeks of treatment in patients 6 to 11 years old. Changes from baseline in average morning and evening instantaneous TNSS (iTNSS) in children 6 to 11 years old and average rTNSS and iTNSS in children 4 to 11 years old were assessed during the first 6 weeks of treatment. RESULTS: Improvements were significantly greater with BDP nasal aerosol than with placebo during the first 6 weeks of treatment in children 6 to 11 years old in average morning and evening rTNSS and iTNSS (mean treatment difference -0.66 [P = .002] and -0.58 [P = .004], respectively). Improvements in average morning and evening rTNSS and iTNSS also were significantly greater in patients 4 to 11 years receiving BDP nasal aerosol than with placebo during the first 6 weeks of treatment (P = .002 and P = .004, respectively). Similar improvements were seen during 12 weeks of treatment. The safety profile of BDP nasal aerosol was comparable to that of placebo. CONCLUSION: The BDP nasal aerosol at 80 µg/day in children 4 to 11 years old was well tolerated and effective in controlling nasal symptoms of PAR. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT01783548.

Flunisolide hydrofluoroalkane with integrated spacer for treating asthma: an updated review.

Flunisolide hydrofluoroalkane (HFA) with integrated spacer is the most recent reformulated inhaled corticosteroid (ICS) for asthma available in the United States. It is the only product that combines a corticosteroid extrafine aerosol with a built-in spacer. The potential clinical benefit of the flunisolide HFA formulation and its integrated spacer for treating persistent asthma was assessed through a comprehensive review of the published literature and data from the past 10 years focusing on (1) flunisolide, the molecule, and the impact of the HFA reformulation; (2) updated information on the anti-inflammatory response to flunisolide HFA, particularly in the distal airways; and (3) the usefulness of an integrated spacer. Flunisolide HFA was found effective and safe in clinical studies and comparable with the chlorofluorocarbon (CFC) formulation, but at about one-third the dose of flunisolide CFC, likely reflecting both the device and the particle size of the reformulated product. Compared with the CFC formulation, the extrafine aerosol and smaller particle size of flunisolide HFA substantially increased pulmonary deposition and decreased oropharyngeal deposition. The integrated spacer further enhanced the pulmonary/oropharyngeal deposition ratio. Examination of lung biopsy specimens indicated a favorable anti-inflammatory response to flunisolide HFA in peripheral airways. Pediatric studies showed no significant effects on growth. The data indicate that flunisolide HFA is a safe and effective maintenance therapy for asthma patients. The integrated spacer may provide an added advantage for patients, especially those who may be more likely to experience adverse effects of ICSs, both local and systemic, including children susceptible to adverse effects on growth.

Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide.

Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov.

Particle size and small airway effects of mometasone furoate delivered by dry powder inhaler.

Inhaled corticosteroids administered by dry powder inhaler (DPI) or metered-dose inhaler are potent anti-inflammatory agents recommended for management of persistent asthma. Respiratory pharmacotherapy is unique in that proper delivery of the medication can be as important as the medication that is delivered. This study was designed to assess the mass median aerodynamic diameter (MMAD) of mometasone furoate (MF) particles from the 100- and 200-microgram/inhalation strength Twisthhaler (Merck & Co., Inc., Whitehouse Station, NJ) and to examine clinical effects of MF-DPI on midexpiratory flow. The MMAD with 100- and 200-microgram Twisthaler inhalers was analyzed using an Anderson cascade impactor. Clinical trial data for MF-DPI administered q.d. in the evening (P.M.) in adults and adolescents aged ≥12 years, as well as children aged 4-11 years, were examined post hoc for changes in forced expiratory flow between 25 and 75% of vital capacity (FEF(25-75)). The average MMAD of the 100-microgram strength Twisthaler (n = 24) was 2.0 micrometers; the average MMAD of the 200-microgram strength Twisthaler (n = 24) was 2.2 micrometers. In adults and adolescents (n = 1149), significant improvements in FEF(25-75) occurred with MF-DPI administered q.d. P.M. versus placebo (p ≤ 0.05). In children (n = 296), FEF(25-75) improved significantly with MF-DPI at 100 microgram q.d. P.M. versus placebo at day 4 and every visit thereafter (p ≤ 0.05). In vitro study suggests that the particle size of MF is optimal (~2 micrometers) for efficient lung deposition when administered via the Twisthaler. Furthermore, randomized, controlled trials provide clinical evidence that MF-DPI q.d. treatment improves small airway function in patients with mild persistent or moderate asthma.

A patient preference and satisfaction study of ciclesonide nasal aerosol and mometasone furoate aqueous nasal spray in patients with perennial allergic rhinitis.

Patients' preference and satisfaction with their nasal allergy medications may be influenced by their sensory attributes. This study evaluates patient preference and satisfaction with ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) compared with mometasone furoate aqueous nasal spray (MFNS). Symptomatic subjects with perennial allergic rhinitis (PAR) were randomized to CIC-HFA at 74 micrograms or MFNS at 200 micrograms q.d. in an open-label, two-period, crossover study. Subject preference was recorded as total preference score (TPS; average of 17 individual preference items) at the end of treatment period 2, and satisfaction was assessed with a 76-item, self-administered instrument at baseline and at the end of each 2-week treatment period. The primary assessments were TPS and regimen attributes composite satisfaction score composed of two of nine satisfaction subscales: sensory impact (including medication running out of the nose, medication running down the throat, and impact on smell and taste) and regimen management (comprised of issues relating to dosing and ability to remember to take medication). Two hundred ninety-four subjects completed the study. A total of 68.1% of subjects preferred CIC-HFA (p < 0.0001 versus MFNS), with a mean TPS of 68.3 versus 31.7 for the MFNS group. The regimen attributes composite satisfaction score significantly (p < 0.0001 for each treatment period) favored CIC-HFA versus MFNS at the end of treatment period 1 (85.5 vs 77.6) and treatment period 2 (83.0 versus 73.5), respectively. In this study, subjects reported higher preference for and satisfaction with CIC-HFA compared with MFNS, suggesting significant differences in patient perception of attributes in favor of CIC-HFA. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01401465.

A double-blind, placebo-controlled trial of the efficacy and safety of two doses of azelastine hydrochloride in perennial allergic rhinitis.

Background: Azelastine hydrochloride (AZE) is a selective, non-sedating H1 antagonist with anti-inflammatory and mast cell stabilizing properties, which can be used as an alternative to intranasal corticosteroids. The objective of this study was to evaluate the efficacy of the new formulation of 0.15% AZE compared to that of the placebo at a dosage of two sprays per nostril twice daily for 4 weeks in patients with perennial allergic rhinitis (PAR). Materials and methods: A total of 581 subjects were randomized in this double-blind (DB) placebo-controlled trial (NCT00712920) that compared 0.10% (1,096 µg daily) and 0.15% AZE (1,644 µg daily) to the placebo in PAR patients. The study consisted of a 7-day single-blind placebo lead-in period and a 28-day DB treatment period. The primary endpoint was the change from baseline in the 12-h reflective total nasal symptom score (rTNSS) for the entire 28-day study period of 0.15% AZE, two sprays per nostril BID compared to the placebo. The efficacy and safety of 0.15% AZE were compared to the placebo. Results: Least square (LS) mean improvement from baseline in the morning (AM) and evening (PM) combined rTNSS was statistically significant for the 0.15% AZE group (p = 0.04) compared to the placebo group. LS mean improvement from baseline in the AM and PM combined rTNSS was 4.10 (4.26) units for 0.15% AZE and 3.81 (3.99) for 0.10% AZE. For individual symptoms, there was a statistically significant change in the LS mean (p = 0.04) improvement from baseline on the 12-h reflective assessment for the 0.15% AZE group for runny nose. Further numerical improvements were shown for itchy nose, nasal congestion, runny nose, and sneezing compared to the placebo. No deaths or serious adverse events related to the study medication were reported. Conclusion: The present formulation of 0.15% AZE is safe and effective in relieving PAR symptoms. It effectively relieves nasal and non-nasal symptoms. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT00712920.

Efficacy and tolerability study of ciclesonide nasal aerosol in patients with perennial allergic rhinitis.

A new nasal aerosol solution formulation of ciclesonide containing a hydrofluoroalkane propellant (CIC-HFA) delivered via a metered-dose inhaler is currently in clinical development as a potential treatment for allergic rhinitis (AR). This study evaluated the efficacy and tolerability of CIC-HFA 74- or 148-microgram doses compared with placebo in patients with perennial AR (PAR). Patients ≥12 years of age with a ≥ 2-year history of PAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo q.d. in the morning (A.M.) for 26 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), and rhinoconjunctivitis quality-of-life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ of ≥3.00 were evaluated for the first 6 weeks of treatment. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Eleven hundred eleven patients were randomized. CIC-HFA 74- and 148-microgram doses showed statistically significant improvements in rTNSS (least squares [LS] mean change, 0.70 and 0.54, respectively; p ≤ 0.001 versus placebo for both), iTNSS (LS mean change, 0.58 and 0.42, respectively; p < 0.05 versus placebo for both), and RQLQ[S] (LS mean change, 0.55 and 0.37, respectively; p < 0.01 versus placebo for both) from baseline. The overall incidence of TEAEs was comparable between the CIC-HFA treatment groups and placebo. In this study, once-daily treatment with CIC-HFA 74- or 148-micrograms showed statistically significant improvements in nasal symptoms of PAR. Both doses were well tolerated. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT00953147.

Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results.

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-µg peanut protein (Viaskin Peanut 250 µg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n = 294) or placebo (n = 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

The efficacy of intranasal antihistamines in the treatment of allergic rhinitis.

OBJECTIVES: To discuss the new use of intranasal antihistamines as first-line therapies, compare and contrast this class of medication with the traditionally available medications, and discuss the potential for intranasal antihistamines to provide relief superior to second-generation oral antihistamines. DATA SOURCES: Review articles and original research articles were retrieved from MEDLINE, OVID, PubMed (1950 to November 2009), personal files of articles, and bibliographies of located articles that addressed the topic of interest. STUDY SELECTION: Articles were selected for their relevance to intranasal antihistamines and their role in allergic rhinitis. Publications included reviews, treatment guidelines, and clinical studies (primarily randomized controlled trials) of both children and adults. RESULTS: This panel was charged with reviewing the place of intranasal antihistamines in the spectrum of treatment for allergic rhinitis. Intranasal antihistamines have been shown in numerous randomized, placebo-controlled trials to be more efficacious than the oral antihistamines. Although intranasal corticosteroids are considered by some to be superior to intranasal antihistamines, multiple studies have shown an equal effect of the 2 classes of medication. Both intranasal corticosteroids and intranasal antihistamines have been shown to reduce all symptoms of allergic rhinitis. In addition, some intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids. CONCLUSIONS: The future of allergy treatment will likely involve a combination of both intranasal corticosteroids and intranasal antihistamines because of the benefits of local administration and their additive effect on efficacy.

Treatment of persistent asthma with Symbicort (budesonide/formoterol inhalation aerosol): an inhaled corticosteroid and long-acting beta2-adrenergic agonist in one pressurized metered-dose inhaler.

OBJECTIVE: Budesonide/formoterol inhalation aerosol (Symbicort AstraZeneca, Wilmington, Delaware) is an inhaled corticosteroid (ICS) and long-acting beta(2)-adrenergic agonist (LABA) combination administered twice daily via one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) approved in the United States for the long-term maintenance treatment of persistent asthma in patients >or=12 years of age whose asthma cannot be controlled by an ICS alone. The objective was to review efficacy, safety, and pharmacogenetic data on budesonide/formoterol pMDI in the treatment of persistent asthma. METHODS: The authors searched PubMed and respiratory meeting databases to identify asthma studies of budesonide/formoterol pMDI. Studies involving traditional and patient-reported outcomes, safety, tolerability, or pharmacogenetics were included. RESULTS: In two 12-week pivotal trials in adolescents and adults, treatment with budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg) twice daily for moderate to severe persistent asthma or 80/4.5 microg x 2 inhalations (160/9 microg) twice daily for mild to moderate persistent asthma, demonstrated greater efficacy and similar tolerability compared with placebo and the same nominal dose of its monocomponents. Comparisons with formoterol dry powder inhaler (DPI) for predose forced expiratory volume in one second (FEV(1)) and with budesonide pMDI for 12-hour mean postdose FEV(1) demonstrated the anti-inflammatory and bronchodilatory contributions of budesonide and formoterol, respectively. Evaluations of patient-reported outcomes, including asthma-specific quality of life and treatment satisfaction, further supported the clinical benefits of budesonide/formoterol pMDI. In a 52-week tolerability study of patients aged >or=12 years, budesonide/formoterol pMDI was delivered at up to double the maximum dose (640/18 microg twice daily) and demonstrated a safety profile similar to that of budesonide (640 microg twice daily), with no unexpected pattern of abnormalities. Additional studies reported that budesonide/formoterol pMDI 320/9 microg twice daily and fluticasone propionate/salmeterol DPI 250/50 microg twice daily have similar efficacy and tolerability, with significantly more patients achieving >or=15% improvement in FEV(1) within 15 minutes with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI. Moreover, inheritance of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor does not appear to affect clinical outcomes with budesonide/formoterol pMDI. CONCLUSION: Budesonide/formoterol pMDI administered twice daily is effective and generally well tolerated in patients whose asthma is not well controlled on ICS alone.

Efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler: randomized controlled trial comparing once- and twice-daily dosing in patients with asthma.

Asthma guidelines recommend titrating maintenance medications to the lowest effective dose. This study assessed the efficacy and tolerability of reducing the frequency of dosing in patients previously controlled with twice-daily budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) to once-daily regimens of BUD/FM pMDI or BUD pMDI. This was a 12-week, randomized, double-blind, double-dummy, placebo (PBO)/active-controlled, multicenter study (N = 752) of patients aged > or =16 years with mild to moderate asthma. After 4-5 weeks on single-blind BUD/FM pMDI 160/9 micrograms twice daily (320/18 micrograms daily), patients with stable asthma received BUD/FM pMDI 160/9 micrograms twice daily (320/18 micrograms daily; morning and evening), BUD/FM pMDI 320/9 micrograms once daily (evening), BUD/FM pMDI 160/9 micrograms once daily (evening), BUD pMDI 320 micrograms once daily (evening), or PBO. BUD/FM (once or twice daily) was more effective (p < or = 0.003) than BUD and PBO on evening peak expiratory flow (primary variable), morning pulmonary function assessments, daily symptoms, and nighttime rescue medication use. Twice-daily BUD/FM was more effective (p < or = 0.05) than both once-daily doses for evening pulmonary function assessments and daytime rescue medication use. All treatments were well tolerated. Once- or twice-daily BUD/FM showed better efficacy than BUD once daily or PBO; results generally were more favorable with twice-daily dosing compared with both once-daily dosing regimens, which had one-half the daily FM dose.

The safety and clinical benefit of budesonide/formoterol pressurized metered-dose inhaler versus budesonide alone in children.

Few studies have evaluated inhaled corticosteroid (ICS)/long-acting beta(2)-adrenergic agonist combination therapy in asthmatic children. This study was designed to evaluate the safety (primary) and clinical benefits (secondary) of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (DPI) in children with persistent asthma. This was a 26-week, multicenter, randomized, open-label U.S. study of 187 children 6-11 years of age previously receiving ICS. After 1 week of usual ICS therapy, subjects received twice-daily budesonide/formoterol pMDI 160/4.5 micrograms x 2 inhalations (320/9 micrograms; n = 124) or budesonide DPI 200 micrograms x 2 inhalations (400 micrograms [320 micrograms delivered ex-mouthpiece]; n = 63). Budesonide/formoterol and budesonide were well tolerated with a similar incidence of adverse events (AEs) (84.6% and 85.7%, respectively), most of mild or moderate intensity. Treatment-related AE incidence was low (5.4%) and similar across groups (budesonide/formoterol, 4.9%; budesonide, 6.3%). No clinically important treatment differences were observed for 12-lead electrocardiograms, hematology, serum glucose and potassium, and 24-hour urinary cortisol. Compared with budesonide, budesonide/formoterol decreased health care use (urgent care visits and interference with daily activities [child] or work [caregiver]; p < or = 0.012) and improved health-related quality of life (Pediatric Asthma Quality of Life Questionnaire [standardized] and Pediatric Asthma Caregiver Quality of Life Questionnaire overall scores; p < or = 0.006) and pulmonary function (predose forced expiratory volume in 1 second and forced expiratory flow during the middle half of exhalation; p < or = 0.007). In this 26-week study of asthmatic children (6-11 years), safety profiles were similar and clinical benefits were greater with budesonide/formoterol than with budesonide.

Evaluation of in vitro Penetration of Fluticasone Propionate from MP-AzeFlu and Fluticasone Propionate Nasal Spray Through EpiAirway™606 Tissues Using Vertical Diffusion Cells.

PURPOSE: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model. MATERIALS AND METHODS: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway™606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 µL of MP-AzeFlu (3.65 µg; n = 8) and 10 µL of FP nasal spray (5.00 µg; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry. RESULTS: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells. CONCLUSION: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief.

Safety and efficacy of olopatadine hydrochloride nasal spray 0.6% in pediatric subjects with allergic rhinitis.

Olopatadine (OLO) nasal spray 0.6% is indicated for treatment of seasonal allergic rhinitis (SAR) in subjects > or = 12 years of age. This study was designed to present the results of two studies that evaluated the efficacy, safety, and pharmacokinetics (PK) of OLO in children with allergic rhinitis (AR). These were multicenter, double-blind, randomized, parallel-group studies in subjects 6 to <12 years of age (study 1) and 2 to <6 years of age (study 2) with SAR (study 1) or AR (study 2). In study 1, nasal and ocular symptoms were scored for efficacy, and study 2 included PK analyses. In both studies, subjects were evaluated based on physical/nasal examinations and adverse events (AEs). Overall, 1188 subjects (study 1) and 132 subjects (study 2) were randomized, respectively. OLO (1 or 2 sprays/nostril, b.i.d.) was superior to vehicle in the percent decrease in reflective total nasal symptom scores (p < or = 0.0120). OLO 1 spray/nostril b.i.d. was also superior to vehicle in the percent decreases in reflective total ocular symptom scores (p < or = 0.0084), change from baseline in Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire scores (p < or = 0.0377), Caregiver Treatment Satisfaction Questionnaire scores (p < or = 0.0450), and proportions of subjects reporting improvements in Subject Global Assessments (p = 0.0035). The most frequently reported treatment-related events in the OLO group were bad/bitter taste and epistaxis. In subjects 6 to <12 years of age, OLO was superior to vehicle in the treatment of SAR. In subjects 2 to <12 years of age, OLO had an overall low rate of AEs and low systemic exposure.