fluticasone-furoate and Rhinitis--Allergic--Perennial

To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR).. A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2-12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen's guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of -0.20, effects were considered clinically significant.. Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD -0.18; 95 percent CI -0.35 to -0.01,. The currently available evidence suggests that FFNS, 110 μg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

Topics: Androstadienes; Anti-Allergic Agents; Child; Humans; Nasal Sprays; Rhinitis, Allergic, Perennial; Treatment Outcome

Fluticasone furoate (FF) is the latest glucocorticoid officially approved for the treatment of allergic rhinitis. FF has shown the highest affinity and selectivity for the glucocorticoid receptors as well the longest tissue retention compared with other available intranasal steroids; these new pharmacologic characteristics provide the basis for its potent and prolonged anti-inflammatory activity at the target site.. A literature review achieved through PubMed and Medline research methods supports the clinical efficacy of FF versus placebo in reducing ocular and nasal symptoms related to allergic rhinitis (at the recommended starting doses of 110 μg once daily for adults and adolescents and 55 μg once daily for children), with a good safety profile. Moreover, the present review also compares FF with other intranasal steroids: FF represents a molecular evolution of fluticasone propionate (FP), and there is scientific evidence of therapeutic advantages over FP.. Fluticasone furoate is a promising molecule in the treatment of allergic rhinitis as it fits fully all the official guidelines' criteria. It is now being considered as a topical steroid that is quite close to the ideal pharmacological model for glucocorticoids due to its satisfying safety/tolerability profile, both in adults and children, leads FF to be considered as a topical steroid that is quite close to the ideal pharmacologic model for glucocorticoids. More studies should be directed to assess the improvement of quality of life in subjects with allergic rhinitis treated with FF, in comparison with other intranasal steroids and even H1-antihistamines; in addition, it could be also interesting to analyze eventual, additional effects of FF in patients with bronchial asthma, which is frequently associated with allergic rhinitis.

Topics: Androstadienes; Anti-Inflammatory Agents; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate is a novel enhanced-affinity corticosteroid that has demonstrated favourable safety and tolerability in paediatric patients. Three pivotal phase III studies were conducted in children as young as 2 years of age; however, because the European Medicines Agency has recently approved fluticasone furoate for use in children aged>or=6 years, a subanalysis has been conducted to support safety and tolerability in the 6- to 11-year age group.. All three trials included in the subanalysis were randomized, double-blind, placebo-controlled, parallel-group studies: a 2-week US study in patients with seasonal allergic rhinitis (SAR), a 12-week global study in patients with perennial allergic rhinitis (PAR) and a 6-week US hypothalamic-pituitary-adrenal (HPA) axis safety study in patients with PAR. Randomized patients received once-daily treatment with either fluticasone furoate nasal spray (FFNS) 55 microg (n=297; 2-week SAR and 12-week PAR studies only), FFNS 110 microg (n=321) or vehicle placebo nasal spray (n=330). Safety assessments included clinical adverse event (AE) monitoring, clinical laboratory tests, detailed nasal examinations, monitoring of vital signs, and 12-lead ECGs. Ophthalmic examinations (12-week PAR study only) were conducted by an ophthalmologist or optometrist before randomization and at final treatment visit. Twenty-four-hour urinary cortisol (UC) excretions (6- and 12-week PAR studies) and serum cortisol (SC) concentrations (6-week PAR study only) were assessed at specified timepoints over 24 hours as a measure of HPA axis function. In the 6-week HPA axis safety study in patients with PAR, 24-hour UC and SC samples were collected in a domiciled (clinical) setting.. No unexpected safety results were observed in patients aged 6-11 years enrolled in the three studies. Across all three trials, AEs considered by the investigator to be drug related were observed in 10%, 7% and 8% of patients in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively. The most common AEs were headache (8%, 9% and 8% in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively), nasopharyngitis (5%, 6% and 5%, respectively), pharyngolaryngeal pain (5%, 3% and 4%, respectively), epistaxis (4% in both active treatment groups and 4% in the placebo group) and pyrexia (3% in both active treatment groups and 2% in the placebo group). Findings from nasal examinations were similar across the treatment and placebo groups. Ophthalmic examinations found no differences between the treatment groups for mean change from baseline in intraocular pressure (assessed in the 12-week PAR study only), and no posterior subcapsular cataracts were reported in patients in either FFNS-treatment group. In the 6-week HPA axis study, 24-hour SC geometric mean concentrations were similar for FFNS and placebo groups. The lower limit of two-sided 95% confidence interval (CI) for the treatment ratio was greater than the prespecified noninferiority margin of 0.8 (treatment ratio=0.92, 95% CI 0.80, 1.05).. FFNS has a favourable safety and tolerability profile in patients aged 6-11 years with PAR or SAR.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Aerosols; Androstadienes; Anti-Allergic Agents; Child; Female; Humans; Hydrocortisone; Male; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate is a novel glucocorticoid developed for the treatment of allergic rhinitis and other inflammatory diseases. Fluticasone furoate demonstrates high systemic clearance, low oral bioavailability and low absolute bioavailability after intranasal administration (<0.5%). The drug possesses a high receptor affinity. Fluticasone furoate is given once daily at a dose of 110 microg. Clinical studies tested the efficacy of fluticasone furoate in seasonal allergic rhinitis and perennial allergic rhinitis. Patients randomized to the drug experienced significant alleviation in their nasal and ocular symptoms as well as clinically relevant improvement in quality of life. The drug is well tolerated and has a good safety profile owing to reduced systemic exposure. Thus, fluticasone furoate might represent a single treatment option for nasal and ocular symptoms of allergic rhinitis.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Glucocorticoids; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate nasal spray is a new topical intranasal corticosteroid with enhanced affinity for the glucocorticoid receptor and low systemic exposure, which was recently approved in the US for the treatment of seasonal or perennial allergic rhinitis in adults and in children aged >or=2 years. Fluticasone furoate nasal spray employs a novel delivery device with a unique side-actuated design, a short nozzle and a new trigger mechanism designed for ease of use. In well controlled clinical trials, intranasal fluticasone furoate 110microg once daily for 2 weeks in adults and adolescents with seasonal allergic rhinitis reduced nasal and ocular symptoms, and improved health-related quality of life to a significantly greater extent than placebo. Similarly, treatment with intranasal fluticasone furoate 110microg once daily for 4-6 weeks in adults and adolescents with perennial allergic rhinitis was superior to placebo in reducing nasal symptoms and with respect to overall response to therapy. In children aged 6-11 years, fluticasone furoate nasal spray was shown to be effective in reducing the nasal symptoms of seasonal and perennial allergic rhinitis following treatment for 2 and 4 weeks, respectively. Fluticasone furoate nasal spray was well tolerated in adults, adolescents and children aged 2-11 years, with an overall incidence of adverse events similar to that with placebo.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Equipment Design; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Devices for the aqueous delivery of intranasal corticosteroids to patients with allergic rhinitis have been available since 1984, so there is a need for new devices to be developed to provide ease of use, efficacy and safety. A novel drug delivery system has been developed for fluticasone furoate (FF; GlaxoSmithKline): a new enhanced-affinity glucocorticoid with a scent-free formulation. The FF system was developed, giving attention to patients' unmet needs, in order to promote acceptance and compliance. It demonstrates a number of key features including its ergonomic design, side-actuation system and short delivery nozzle. Exploiting issues with present devices highlighted the need for the FF system. This review reports data from key studies and surveys conducted by GlaxoSmithKline during development, to determine ease of use and acceptance of the FF system. Findings suggest that the FF system should aid in improving attitudes to the use of intranasal corticosteroids amongst physicians and patients.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Drug Delivery Systems; Humans; Patient Compliance; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed for the treatment of allergic rhinitis (AR). This study aimed to assess the safety, efficacy, and systemic exposure of FFNS in Japanese children with perennial AR (PAR).. In this multicentre, open-label, phase 3 study, 61 children aged 2 to <15 years were treated with FFNS 55 μg, once daily for 12 weeks. Nasal and ocular symptoms were scored by parents/guardians/patients and recorded in a patient's daily diary. In addition, rhinoscopy findings, including mucosal swelling, were scored by the investigators as an efficacy measure. As a safety measure, adverse events and clinical laboratory data were evaluated.. An adverse event was reported by 67% of patients during the treatment and follow-up period, all of which were mild in intensity. The most commonly reported adverse events were nasopharyngitis and acute sinusitis (acute rhinosinusitis). There were no serious adverse events. FFNS 55 μg improved nasal symptom scores and rhinoscopy findings compared with the baseline. Ocular symptom scores were also improved compared with the baseline in FFNS 55 μg in a sub-group of patients with any ocular symptoms at baseline. FFNS 55 μg was shown to be well tolerated over the 12-week treatment period. Majority of patients receiving FFNS 55 μg had unquantifiable plasma levels of fluticasone furoate (FF).. Twelve-week treatment with FFNS 55 μg, once daily, is well tolerated and effective with low systemic exposure in Japanese children aged 2 to <15 years with PAR.

Topics: Adolescent; Androstadienes; Asian People; Child; Child, Preschool; Female; Humans; Japan; Male; Nasal Sprays; Rhinitis, Allergic, Perennial; Treatment Outcome

Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed for the treatment of allergic rhinitis (AR). This is the first randomized clinical trial to assess the efficacy and safety of FFNS in Japanese children with perennial AR (PAR).. In this multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study, 261 children aged 6 to <15 years were treated with FFNS 55μg, once daily or placebo for two weeks. Nasal and ocular symptoms were rated by parents/guardians/patients in the patient daily diary. The primary endpoint was the mean change from baseline in the three total nasal symptom score (3TNSS). In addition, rhinoscopic findings were rated by the investigators as an efficacy measure. As a safety measure, adverse events and clinical chemistry and hematology were evaluated.. Mean change from baseline over the entire treatment period in 3TNSS was greater in the FFNS 55μg group compared with placebo, and the difference was statistically significant (p < 0.001). Significant improvements in rhinoscopic findings of swelling of inferior turbinate mucosa and quantity of nasal discharge were also observed. The total ocular symptom score (TOSS) was reduced significantly in the FFNS 55μg group, compared with placebo, in the second week in a subgroup of patients with baseline TOSS > 0. The incidence of adverse events was similar between FFNS 55μg(18%) and placebo (19%).. Two-week treatment with FFNS 55μg, once daily is effective and tolerable in Japanese children aged 6 to <15 years with PAR.

Topics: Androstadienes; Asian People; Child; Child, Preschool; Female; Humans; Infant; Japan; Male; Nasal Sprays; Rhinitis, Allergic, Perennial; Time Factors; Treatment Outcome

This is the first study, to our knowledge, to evaluate the ocular effects of an intranasal corticosteroid during 2 years of treatment for perennial allergic rhinitis (PAR).. To assess ocular safety in adult and adolescent patients 12 years and older with PAR after 2 years of continuous treatment with fluticasone furoate nasal spray (FFNS), 110 μg once daily, and placebo.. This was a 2-year, randomized, double-blind, placebo-controlled study of once-daily FFNS, 110 ìg, and placebo in 548 patients 12 years and older with PAR. The primary ocular safety end points were time to first occurrence of an event for the Lens Opacities Classification System, Version III (LOCS III), posterior subcapsular opacity (PSO) and time to first occurrence of an event for intraocular pressure (IOP).. On the basis of survival analyses, the difference between the treatment groups for time to first occurrence of a LOCS III PSO and time to first occurrence of an IOP event was not statistically significant (P = .39 and P = .34, respectively). Changes from baseline in visual acuity, LOCS III PSO, cortical opacity, LOCS III nuclear opacity and nuclear color, IOP, and horizontal cup-to-disc similar between treatment groups. There were no ophthalmic-related adverse events of LOCS III PSO or IOP that led to early withdrawal. The most common drug-related adverse event was epistaxis (FFNS, 28%; placebo, 14%).. These data neither support nor negate current recommendations for regular ophthalmic monitoring in patients treated with intranasal corticosteroids.. clinicaltrials.gov Identifier: NCT00682643.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Cataract; Child; Double-Blind Method; Epistaxis; Female; Humans; Intraocular Pressure; Male; Middle Aged; Nasal Sprays; Rhinitis, Allergic, Perennial; Treatment Outcome; Young Adult

In clinical trials, only about 60% of subjects report an excellent response to intranasal steroids, suggesting a need to add therapies to intranasal steroids to provide additional efficacy.. To determine whether the combination of fluticasone furoate and oxymetazoline is more efficacious than either agent alone, and to determine whether rhinitis medicamentosa develops after treatment.. We performed a double-blind, double-dummy, randomized, placebo-controlled parallel study. Sixty patients with perennial allergy were randomized to 4 weeks of once-a-night treatment with fluticasone furoate, oxymetazoline hydrochloride, the combination, or placebo. They were monitored during treatment and for 2 weeks posttreatment.. The total nasal symptom score over the 4 weeks of treatment was lower with the combination (median, 143; range, 30-316) compared with treatment with placebo (262; 116-358) and oxymetazoline alone (219; 78-385; ANOVA, P = .04). When acoustic rhinometry was compared between the groups at the end of 4 weeks of treatment, the combination resulted in significantly higher nasal volume (mean + SEM, 15.8 + 1.1 mL; P< .03) compared with both placebo (12.1 + 0.9 mL) and oxymetazoline (12.4 + 0.8 mL) alone. The quality of life data showed no significant differences among the groups. Peak flow showed a nonsignificant improvement with the groups on fluticasone furoate. There was no evidence of rhinitis medicamentosa.. The addition of oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. The lack of development of rhinitis medicamentosa suggests the need for a large multicenter study to develop a once-a-day combination of an intranasal steroid and a long-acting topical decongestant.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Nasal Decongestants; Oxymetazoline; Rhinitis, Allergic, Perennial

The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary-adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 microg QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR.

Topics: Administration, Intranasal; Androstadienes; Child; Child, Preschool; Double-Blind Method; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Rhinitis, Allergic, Perennial

Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated.. To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR.. A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate.. A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment.. Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Prednisolone; Rhinitis, Allergic, Perennial; Treatment Outcome

Intranasal corticosteroids are recommended as first-line therapy for the treatment of allergic rhinitis. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of allergic rhinitis.. To compare the efficacy and safety of intranasal fluticasone furoate with those of vehicle placebo nasal spray in adult and adolescent patients with perennial allergic rhinitis (PAR).. After screening (7-14 days), patients 12 years and older with confirmed PAR were randomized to receive fluticasone furoate, 110 microg once daily, or placebo once daily intranasally for 4 weeks in this double-blind, multicenter study. The primary end point was mean change from baseline during the entire treatment period in daily reflective total nasal symptom score (rTNSS), recorded on diary cards by patients, using a 4-point categorical scale.. The mean reduction from baseline during the treatment period in daily rTNSS was significantly greater in fluticasone furoate recipients than in placebo recipients (P = .005). This finding was supported by significantly greater mean reductions in morning rTNSS and evening rTNSS (P = .004 and P = .011, respectively). A significantly greater mean reduction in instantaneous morning predose TNSS with fluticasone furoate compared with placebo (P = .006) confirmed the efficacy of once-daily administration. Fluticasone furoate was also significantly more effective than placebo in overall response to therapy (P = .005).. Fluticasone furoate nasal spray, 110 microg once daily, effectively relieved nasal symptoms of PAR in adults and adolescents 12 years and older.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Quality of Life; Rhinitis, Allergic, Perennial; Surveys and Questionnaires; Treatment Outcome

Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR).. The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR.. This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment.. Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF.. In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Mucosa; Odorants; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sensation; Sensory Thresholds; Surveys and Questionnaires; Taste; Treatment Outcome; United States

It is essential to assess potential growth effects of any newly developed corticosteroid. Fluticasone furoate is a recently approved, enhanced- affinity intranasal corticosteroid with low systemic bioavailability and proven efficacy in treating allergic rhinitis.. The aim of the current study was to assess whether treatment with fluticasone furoate nasal spray affected the short-term lower-leg growth rate in children with allergic rhinitis.. Prepubertal children with seasonal or perennial allergic rhinitis of at least 1 year's duration were included in this single-center, randomized, double-blind, placebo-controlled, crossover study. The study consisted of 4 periods, each of 2 weeks' duration screening, then 2 treatment periods separated by a washout). Study medications were fluticasone furoate nasal spray 110 microg and placebo nasal spray, both administered QD in the morning. The primary end point, lower-leg growth rate (measured in millimeters per week), was assessed by knemometry. Adverse events were also assessed.. Fifty-eight patients were randomized to the study and comprised the intent-to-treat (ITT) population (mean [SD] age, 9.1 [1.4] years; 39 males, 19 females). Five patients were excluded from the ITT group due to protocol violations; thus, 53 patients (mean [SD] age, 9.0 [1.4] years; 35 males, 18 females) comprised the growth population (a de facto per-protocol group). In the growth population, the adjusted mean lower-leg growth rate was 0.40 and 0.42 mm/wk with fluticasone furoate and placebo, respectively. The difference in adjusted mean lower-leg growth rate between fluticasone furoate and placebo was -0.016 mm/wk (95% CI, -0.13 to 0.10). Fluticasone furoate was noninferior to placebo, as the lower boundary of the 95% CI was above the prespecified noninferiority margin of -0.20 mm/wk. These results were supported by the ITT analysis. Fluticasone furoate nasal spray was well tolerated and had an adverse-event profile similar to that of placebo nasal spray. Nasopharyngitis (placebo, 4; fluticasone furoate, 1) and headache (placebo, 3; fluticasone furoate, 1) were the most frequent adverse events during the treatment periods.. In this study, fluticasone furoate nasal spray 110 microg QD for 2 weeks had no effect on lower-leg growth rate in these prepubertal children with allergic rhinitis.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Aerosols; Androstadienes; Child; Cross-Over Studies; Double-Blind Method; Female; Growth and Development; Growth Disorders; Humans; Lower Extremity; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Time Factors; Treatment Outcome

Intranasal corticosteroids (INS) are the first line treatment for allergic rhinitis (AR). To guide clinical decision-making, we created a therapeutic index (TIX) for INS reflecting efficacy and safety.. A Medline search (1966 to June 2009) was carried out to identify all placebo-controlled randomized trials, and observational reports for safety issues, with Dexamethasone, Budesonide (BUD), Fluticasone propionate (FP), Fluticasone furoate (FF), Flunisolide, Mometasone furoate (MF), Triamcinolone (TRIAM), and Beclomethasone dipropionate (BDP) as treatment for AR. Data on three efficacy (nasal symptoms, ocular symptoms, global assessment) and three safety outcomes (epistaxis, growth, systemic ocular effects) were extracted. Meta analyses were performed for each INS and outcome and results were categorised into scores by quartiles. Scores of the three efficacy and safety outcomes were summed up to create summation scores for efficacy (ES) and side effects (AES), respectively with a maximum of 9 points. The TIX was then defined as the ratio of ES and AES.. Data of 84 studies were extracted. Based on availability of data, a TIX was calculated for 6 substances. BUD showed the highest efficacy score followed by MF and TRIAM. The lowest scores for side effects were achieved by MF and TRIAM followed by FP. These findings resulted in TIX scores of 7 and 5 for MF and TRIAM, respectively, indicating a high efficacy and low potential of adverse events. Medium scores were reached by BUD and FP and lower scores by BDP and FF.. Although safety and efficacy is proven for all available INS by multiple studies, the systematic aggregation and analysis of data allows for a differentiated summary on clinically important features.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Treatment Outcome; Triamcinolone

Fluticasone furoate is a novel glucocorticoid receptor agonist marketed as a treatment for seasonal and perennial allergic rhinitis. Forced degradation of fluticasone furoate under conditions of light led to a number of degradation products, the structures of which were elucidated using mass spectrometry and a range of one and two-dimensional NMR experiments. Three structures were derived, including two which involved a rearrangement of the steroid ring A to give cross-linked degradation products. The results demonstrate the applicability of a previously observed mechanism of photodegradation to fluticasone furoate.

Topics: Androstadienes; Anti-Allergic Agents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Molecular Structure; Photolysis; Receptors, Glucocorticoid; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Interactions; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome