Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo

BACKGROUND: Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established. OBJECTIVES: To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis. METHODS: In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring. RESULTS: Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.     

A pilot study on the efficacy of mometasone furoate fatty cream on clinical parameters, time to relapse and microbial flora in atopic dermatitis

Aim To study the antimicrobial effect in vitro of hexylene glycol and mometasone furoate fatly cream (contains 12% hexylene glycol) and to study the effect of mometasone furoate fatty cream on clinical parameters and microbial flora in patients with atopic dermatitis. Methods The effect of hexylene glycol and mometasone furoate fatty cream against Staphylococcus aureus, S. epidermidis, Pityrosporum ovule and Candida albicans was studied in vitro. Twenty patients with moderate to severe atopic dermatitis were treated with mometasone furoate 0.1 % fatty cream once daily for 3 weeks and then intermittently for 3 weeks. Quantitative cultures for bacteria and fungi were taken at baseline, during treatment and 4 weeks after end of treatment. Results Both hexylene glycol and mometasone furoate fatty cream were effective in vitro against the studied microorganisms. Thirteen of 18 patients who returned for control were cleared after 3 weeks of treatment and 15/18 patients or 83% were cleared after 6 weeks. Four weeks after end of treatment only one patient remained cleared. However, 11/14 patients who returned for this control were still improved compared to baseline. S aureus was cultured in 16/20 patients at baseline but in only 7/18 patients after 6 weeks of treatment. The number of S. aureus dropped significantly but increased two-fold 4 weeks after end of treatment. The number of cultured P. ovale was also significantly reduced after 6 weeks. Conclusion This study clearly demonstrate the good effect of mometasone furoate fatty cream, which contains 12% hexylene glycol, in the treatment of atopic dermatitis paralleled by a significant reduction in the number of S. aureus and P. ovale.     

Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate

AIM: Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%. We hypothesize that FP and MF have comparable systemic availabilities that can explain their potential to cause systemic effects. METHODS: Steady-state FP and MF trough plasma samples were determined from a clinical study by Fardon et al. in patients with persistent asthma (forced expiratory volume in 1 s = 91%). The percent plasma protein binding of FP and MF was measured using ultracentrifugation. Free FP plasma concentrations were normalized for their differences in receptor binding affinity compared with MF and linked to overnight urinary cortisol/creatinine with an inhibitory E(max). RESULTS: A plot of steady-state FP and MF total trough plasma concentrations vs. dose showed that both drugs exhibit dose linearity. MF has comparable bioavailability to FP based on the steady-state concentrations observed for the different doses. The free plasma concentration producing 50% of urinary cortisol suppression (IC(50)) for MF was not statistically different from the free, normalized IC(50) for FP. CONCLUSION: FP and MF have similar pulmonary deposition and the same potential to cause systemic side-effects due to their similar IC(50) values. The observed urinary cortisol suppression of FP and MF is in agreement with their systemic availability, their differences in plasma protein binding and receptor binding affinity.     

Montelukast as an adjuvant to mainstay therapies in patients with seasonal allergic rhinitis

BACKGROUND: Drug selection for optimal treatment of allergic rhinitis may be difficult and involve many diverse factors. OBJECTIVE: To evaluate montelukast, in the treatment of patients with seasonal allergic rhinitis, as an adjuvant to mainstay therapies, i.e., antihistamines and corticosteroids. METHODS: The study was a prospective, three-phased (per lasted 2 weeks) clinical trial. In phase I, patients were separated into two groups, based on the predominating symptoms: (1) runners (patients with moderate to severe sneezing/itchy, watery nose/itchy, watery eyes), and (2) blockers (patients with moderate to severe nasal congestion). The runners received antihistamine loratidine 10 mg daily, and the blockers received intranasal corticosteroid mometasone furoate 200 microg. In phase II, if patients were dissatisfied with the initial treatment, they were assigned to receive another study drug additionally. In phase III, for the patients unsatisfied with the treatment of loratidine plus mometasone furoate, montelukast 10 mg once daily was added. RESULTS: Of the 169 patients who entered phase I, 150 could be evaluated for treatment efficacy and safety. There were 108 runners and 42 blockers. Physicians' and patients' assessments indicated that in phase I 58 runners (60.0% of 50 runners) and 36 blockers (33.3% of six blockers) were satisfied with their therapy. In phase II, 30 runners (27.7%) and two blockers (4.7%) were satisfied with the addition of other study drug. Totally 62.6% of patients were satisfied at the end of phase I, and 84.0% at the end of phase II. Sixteen patients (66.6% of 24 patients) were satisfied with the addition of montelukast to the previous two drugs (in total, 10.6% of patients). Fourteen patients (12.2%) treated with loratadine, and three patients (0.3%) treated with mometasone, reported side-effect. CONCLUSION: The results of this trial indicate that 10% of patients with seasonal allergic rhinitis may be treated with the supplement of montelukast to mainstay therapy.     

Mometasone furoate nasal spray is safe and effective for 1-year treatment of children with perennial allergic rhinitis

Objective

Perennial allergic rhinitis (PAR) affects children at a young age. Current guidelines recommend intranasal corticosteroids as the first-line treatment in patients with moderate-to-severe or persistent disease or in those who have congestion. In this study, the long-term safety and efficacy of mometasone furoate nasal spray (MFNS) were assessed in children with PAR.

Methods

In this multicenter, active-controlled, evaluator-blind, 12-month study, 255 children aged 6-11 years with a ≥1-year history of PAR were randomized to receive once-daily MFNS 100 μg (n = 166) or the active comparator beclomethasone dipropionate (BDP) 168 μg (n = 85). Changes from baseline in overall PAR symptoms and response to treatment were rated at each visit. Cosyntropin stimulation testing, as well as tonometry and slit lamp procedures, were performed. Safety variables were assessed.

Results

A total of 137 subjects in the MFNS group and 68 in the BDP group completed treatment. The mean reductions in physician- and subject-rated overall condition of PAR at week 52 were −42.1% and −39.7%, respectively, for MFNS, compared with −44.0% and −39.0%, respectively, for BDP. A total of 94% and 100% of MFNS and BDP subjects, respectively, reported adverse events (AEs), which were mostly mild or moderate. The most frequently reported treatment-related AEs in both groups were epistaxis, headache, and pharyngitis. Response to cosyntropin was normal and no posterior subcapsular cataracts were observed in either group. Although no significant changes in intraocular pressure were observed with MFNS, one subject receiving BDP demonstrated this effect.

Conclusions

Treatment with MFNS 100 μg once daily for 1 year was well tolerated in children 6-11 years old, with negligible systemic exposure and no evidence of suppression of the hypothalamic-pituitary-adrenal axis or ocular changes.     

糠酸莫米松鼻用即型凝胶剂的制备及质量评价

 目的 制备糠酸莫米松鼻用即型凝胶剂，并建立其质量控制方法。方法 以结冷胶、甲基纤维素为凝胶基质制备糠酸莫米松鼻用即型凝胶剂，采用高效液相色谱法测定糠酸莫米松的含量，并对方法进行考察，建立相应的质量标准。结果 糠酸莫米松在1～100 μg/mL范围内线性关系良好（r=0.9999），平均回收率为100.6％。结论 该制剂工艺简单，质量可控，可满足临床用药需求。     

Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic rhinitis

BACKGROUND: Mometasone furoate nasal spray (MFNS, NASONEX ), is a new synthetic corticosteroid with considerable efficacy in the treatment of seasonal and perennial rhinitis and less than 0.1% systemic absorption. This study was designed to evaluate the time of onset of action of MFNS. The subjects were evaluated over the course of 2 weeks during the spring allergy season. METHODS: The effects of MFNS 200 microg given once daily for 2 weeks were evaluated in a randomized, multicenter, double-blind, placebo-controlled study in 201 patients with seasonal allergic rhinitis. Clinically significant onset of action was assessed prospectively by special patient diary cards kept during the first 3 days of treatment. RESULTS: By 12 h after initial dosage (the earliest evaluation), 28% of patients in the MFNS group experienced clinically significant relief, compared with 13% of those given placebo (P = 0.01). Median time to at least moderate symptom relief in patients who received MFNS was 35.9 h, compared with more than 72 h in patients given placebo (P<0.01). By 72 h, 64% of the patients receiving MFNS experienced at least moderate relief, compared with 40% of those treated with placebo (P<0.01). Both patient and physician ratings of symptom severity, response to treatment, and overall condition of rhinitis indicated significant (P<0.01) superiority of MFNS over placebo. MFNS was well tolerated, with adverse events comparable to placebo. CONCLUSIONS: MFNS provided rapid onset of clinically significant symptom relief in patients with seasonal allergic rhinitis.     

Topical tacrolimus 0.1% ointment (protopic) reverses nickel contact dermatitis elicited by allergen challenge to a similar degree to mometasone furoate 0.1% with greater suppression of late erythema

The aim of this study was to evaluate the ability of topical tacrolimus 0.1% under occlusion for 48 h to suppress nickel-elicited allergic contact dermatitis in a randomized, petrolatum- and mometasone furoate 0.1% ointment-controlled double-blind, intra-individual study which included 28 women volunteers. 3 closed patch tests (Finn Chambers on Scanpor, Epitest Ltd Oy, Tuusula, Finland) containing 0.1 ml of 5% nickel sulfate in petrolatum were applied on day 0. After removal on day 2, the study compounds were applied under occlusion for 48 h. The eczema reaction and the degree of erythema were evaluated clinically and by reflectance spectrophotometry at days 4 and 7, respectively. Mean visual scores corresponding to petrolatum-treated sites were significantly higher than those corresponding to both mometasone furoate and tacrolimus at days 4 (P < 0.001) and 7 (P < 0.001). In both tacrolimus- and mometasone furoate-treated sites, there was a significant decrease in visual scores with time (P < 0.001) from day 2 to day 7, and the corresponding mean decreases in scores were 0.73 and 1.04, respectively. The difference between both was 0.30 in favour of tacrolimus (95% confidence intervals, -0.04 and 0.65), although this did not reach statistical significance (P = 0.084). Mean erythema index values were similar at day 2. Significant differences among treatment sites were seen at days 4 (P < 0.001) and 7 (P < 0.001). The decrease was significantly more pronounced on day 7 in patches where tacrolimus had been supplied (P < 0.5). This method might provide useful means to compare different concentrations and/or presentations of tacrolimus or other calcineurin inhibitors and topical anti-inflammatory agents.     

皮敏消胶囊联合糠酸莫米松治疗寻常型银屑病的疗效观察

目的：观察皮敏消胶囊联合糠酸莫米松软膏治疗寻常型银屑病的临床疗效和安全性。方法123例寻常型银屑病患者分为治疗组、对照1组和对照2组各41例,治疗组患者口服皮敏消胶囊,每天3次,每次4片,外用糠酸莫米松软膏,每天2次,每次1遍,连续治疗8周;对照1组患者口服复方氨肽素片,每天3次,每次5片,外用糠酸莫米松软膏,每天2次,每次1遍,连续治疗8周;对照2组患者外用糠酸莫米松软膏,每天2次,每次1遍,连续治疗8周。结果治疗组患者治疗后有效率为80．49％;对照1组患者治疗后有效率为78．05％;对照2组患者治疗后总有效率为63．41％。治疗组、对照1组与对照2组疗效比较差异均有统计学意义（Z＝-2．359,P＝0．018;Z＝-2．102,P＝0．036）;治疗组与对照1组疗效比较差异无统计学意义（Z＝-0．271,P＝0．787）。三组患者均无明显不良反应。结论皮敏消胶囊联合糠酸莫米松软膏治疗寻常型银屑病是安全的、有效的。     

糠酸莫米松联合抗组胺药物对非变应性鼻炎的疗效观察

目的分析糠酸莫米松联合抗组胺药物治疗NAR的疗效。方法选择本院收治的NAR患者34例,应用糠酸莫米松联合抗组胺药物治疗。分别对患者治疗前、治疗后1个月、治疗后3个月的临床症状进行评估。结果患者治疗前主要症状的评分为(2.71±0.53)分,治疗后1个月为(1.81±0.53)分,治疗后3个月为(0.89±0.43)分;对患者治疗前后分类症状语言评价量表评分比较,9个症状评分均呈下降趋势,差异有统计学意义(P<0.05);在治疗过程中头痛发生率为3.0%(1/33),鼻腔干燥发生率为3.0%(1/33)。结论糠酸莫米松联合抗组胺药物可以有效改善NAR患者的临床症状。