非水性皮质激素喷鼻剂QNASL获批用于鼻过敏

2012年3月26日，Teva制药宣布，美国食品药物管理局(FDA)已批准QNASL(丙酸倍氯米松)用于治疗成人和≥12岁青少年的季节性和常年鼻过敏症状。QNASL是一种非水性的“干性”皮质激素鼻气雾剂，配有一个内置的剂量计算器。
QNASL喷鼻剂的安全性和有效性已在4项3期随机、双盲、平行分组、多中心、安慰剂对照临床试验中得到了验证。在这些试验中，患者使用QNASL 320 μg，1次/d，每次在2个鼻孔各喷2下。
与使用QNASL喷鼻剂相关的最常见不良反应为鼻部不适、流鼻血和头痛。有青光眼或白内障病史的患者在使用QNASL期间应定期接受眼部检查。使用皮质激素的患者可能更容易发生感染。使用QNASL喷鼻剂的患者应避免感染患者，如水痘或麻疹。

制造商：
Teva药厂

类药物：
类固醇。

活性成分（S）：
丙酸倍氯米松80mcg/actuation的非水喷鼻剂soln的。

指示（S）：
季节性和常年性过敏性鼻炎。

药理作用：
丙酸倍氯米松是一个被广泛地转化为活性代谢产物，倍氯米松-17-monopropionate前药。丙酸倍氯米松的影响性鼻炎的症状的确切机制尚不清楚。糖皮质激素已被证明有多个抗炎作用，抑制两种炎性细胞（如肥大细胞，嗜酸性粒细胞，嗜碱性粒细胞，淋巴细胞，巨噬细胞和中性粒细胞）和释放炎症介质（如组胺，花生酸，白三烯和细胞因子）。

临床试验：
已在三个随机，安慰剂控制在2-6个星期的时间与季节性或常年性过敏性鼻炎的症状≥12岁的成人和青少年患者的临床试验评估的有效性和安全QNASL。 3个临床试验，包括2周的剂量不等的季节性过敏性鼻炎患者的试验中，2周，季节性过敏性鼻炎的药效试验，以及一个为期6周的常年性过敏性鼻炎的药效试验。

疗效的评估是根据总的鼻症状评分（TNSS）相较。 TNSS病人的四个人的鼻部症状，1 0-3类别的严重程度量表（0 =无，1 =轻度，2 =中度（流鼻涕，打喷嚏，鼻塞，鼻痒）的得分总和计算， 3 =严重）反射（rTNSS）的或瞬时（iTNSS）。 rTNSS需要记录患者症状的严重程度，在过去的12小时内; iTNSS需要患者症状的严重程度，超过前10分钟记录。早晨和傍晚TNSS分数平均在治疗期间和差异从安慰剂从基线rTNSS的变化的主要疗效终点。在的早晨iTNSS反映在24小时的给药间隔TNSS是显示效果是否保持在24小时给药间隔。在剂量范围试验中，唯一的治疗方法与QNASL导致的320mcg/day剂量与主要疗效终点，rTNSS安慰剂相比在统计学上显着改善。在两个关键的药效试验，每天与QNASL一次治疗导致统计学意义更大的跌幅在rTNSS从基线（季节性= -0.91 [95％CI：-1.3，-0.5，P <0.01）;（多年生= -0.84 95％CI：-1.2，-0.5]，P <0.01）上午iTNSS（季节性= -0.92 [95％CI为：-1.3，-0.5，P <0.01）;（多年生= -0.78 [95％CI为：-1.1，-0.4，p <0.001比安慰剂）。

法律分类：
RX

成人：
2喷洒在每个鼻孔每天一次;每天最多4喷雾剂。

儿童：
不成立的。

警告/注意事项：
避免在最近的鼻中隔溃疡，鼻腔手术，或鼻外伤，直至痊愈。定期监测在鼻黏膜或念珠菌感染，长期使用可能发生的变化。停止，如果出现鼻腔糜烂/溃疡或念珠菌感染的治疗与局部治疗。历史眼压增高，青光眼，和/或白内障;密切留意视力变化。呼吸道结核病。未经治疗的感染（如真菌，细菌，病毒，单纯眼疱疹）。如果接触到麻疹或水痘，考虑抗感染预防性治疗。如果存在肾上腺皮质功能不全，全身糖皮质激素治疗后，更换鼻内皮质类固醇可能会加剧，肾上腺皮质功能不全的症状（例如，精神不振，抑郁）。监测亢进和肾上腺抑制（如果出现中止逐渐）。监测儿童生长的抑制。避免眼睛，嘴巴和脸。怀孕（C类）。哺乳的母亲。

不良反应（S）：
鼻腔不适，鼻出血，头痛，过敏反应（如果出现停止）。

如何提供：
气溶胶8.7克（120致动）

最后更新：
2012年4月30日

QNASL
Manufacturer:
Teva Pharmaceuticals

Pharmacological Class:
Steroid.

Active Ingredient(s):
Beclomethasone dipropionate 80mcg/actuation; non-aqueous nasal spray soln.

Indication(s):
Seasonal and perennial allergic rhinitis.

Pharmacology:
Beclomethasone dipropionate is a prodrug that is extensively converted to the active metabolite, beclomethasone-17-monopro­pionate. The exact mechanism through which beclomethasone dipropionate affects rhinitis symptoms is unknown. Corticosteroids have been shown to have multiple anti-inflammatory effects, inhibiting both inflammatory cells (eg, mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and the release of inflammatory mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines).

Clinical Trials:
The efficacy and safety of QNASL have been evaluated in three randomized, ­placebo-controlled clinical trials of 2–6 weeks’ duration in adult and adolescent patients ≥12 years with symptoms of seasonal or perennial allergic rhinitis. The three clinical trials included one 2-week dose-ranging trial in patients with seasonal aller­gic rhinitis, one 2-week efficacy trial in seasonal allergic rhinitis, and one 6-week efficacy trial in perennial allergic rhinitis.

Assessment of efficacy was based on the total nasal symptom score (TNSS). TNSS is calculated as the sum of the patients’ scoring of the four indi­vidual nasal symptoms (rhinorrhea, sneezing, nasal congestion, and nasal itching) on a 0–3 categorical severity scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe) as reflective (rTNSS) or instantaneous (iTNSS). rTNSS required the patients to record symptom severity over the previous 12 hours; iTNSS required the patients to record symptom severity over the previous 10 minutes. Morning and evening TNSS scores were averaged over the treatment period and the difference from placebo in the change from baseline rTNSS was the primary efficacy endpoint. The morning iTNSS reflects the TNSS at the end of the 24-hour dosing interval and is an indication of whether the effect was maintained over the 24-hour dosing interval. In the dose-ranging trial, only treatment with QNASL at the dose of 320mcg/day resulted in statistically significant improvements compared with placebo in the primary efficacy endpoint, rTNSS. In the two pivotal efficacy trials, once daily treatment with QNASL resulted in statistically significant greater decreases from baseline in the rTNSS (Seasonal = -0.91 [95% CI: -1.3, -0.5], P<0.001); (Perennial = -0.84 [95% CI: -1.2, -0.5], P<0.001) and morning iTNSS (Seasonal = -0.92 [95% CI: -1.3, -0.5], P<0.001); (Perennial = -0.78 [95% CI: -1.1, -0.4],P<0.001) than placebo.

Legal Classification:
Rx

Adults:
2 sprays in each nostril once daily; ­maximum 4 sprays per day.

Children:
Not established.

Warnings/Precautions:
Avoid in recent nasal septal ulcers, nasal surgery, or nasal trauma until healed. Monitor periodically for possible changes in nasal mucosa or Candida infection with long-term use. Discontinue if nasal erosion/ulceration or Candida infection occur (treat with local therapy). History of increased intraocular pressure, glaucoma, and/or cataracts; monitor closely for change in vision. Respiratory tract tuberculosis. Untreated infections (eg, fungal, bacterial, viral, ocular herpes simplex). If exposed to measles or chickenpox, consider anti-infective prophylactic therapy. If adrenal insuffi­ciency exists following systemic corticoste­roid therapy, replacement with intranasal cortico­steroids may exacerbate symptoms of adrenal insufficiency (eg, lassitude, depres­sion). Monitor for hypercorticism and adrenal suppression (if occur discontinue gradually). Monitor for growth suppression in children. Avoid eyes, mouth and face. Pregnancy (Category C). Nursing mothers.

Adverse Reaction(s):
Nasal discomfort, epistaxis, headache; hypersensitivity reactions (discontinue if occurs).

How Supplied:
Aerosol—8.7g (120 actuations)

Last Updated:
4/30/2012