Daxas® 是一种全新的COPD治疗药物。

它以创新的作用机理，一天一次口服对抗COPD炎症。

临床研究证明它可以显著改善COPD患者的肺功能，减少急性加重。

它的上市将会改变现有COPD治疗观念，是呼吸治疗领域里程碑式的产品。

Daxas® 已获欧盟批准，中国正在注册中。

药品名称：罗氟司特
英文名：Roflumilast
化学名称：3-环丙基甲氧基-N-(3，5-二氯吡啶-4-基)-4-(二氟甲氧基)苯甲酰胺
结构式：

分子式：C17H14Cl2F2N2O3
分子量：403.22
CAS：162401-32-3
剂型及规格： 片剂，500mcg
适应症：慢性阻塞性肺疾病。
产品特点：
2010 年7 月欧盟已批准Nycomed 公司罗氟司特（roflumilast，Daxas）上市用于慢性阻塞性肺疾病（COPD）的治疗。本品为选择性磷酸二酯酶4（PDE4）抑制剂，是十多年来首次获得欧盟批准的新一类COPD 治疗药物。美国FDA 于2011年3月1日批准罗氟司特( roflum ilast) 用于治疗重性慢性阻塞性肺病( COPD ), 该药商标名称为Daliresp, 可每日服用, 用于减少COPD 发病频率及减缓症状。

罗氟司特由位于美国圣路易斯的Forest Pharmaceu ticals(为Forest Laborator ies的分公司)生产销售。
COPD 是一种严重的肺部疾病, 可导致呼吸困难, 主要症状包括气喘、慢性咳嗽、多痰等。1 次发作持续时间可长达数周, 可导致肺功能减退, 并伴随严重焦虑症, 甚至增加死亡风险。据美国国家心肺血液研究所研究表明, COPD 是美国第4大死亡病因, 而吸烟是引发COPD 的主要诱因。罗氟司特适用于患有重型COPD 的患者治疗因支气管炎引起的咳嗽和多痰, 但不适用于另一种COPD即原发性肺气肿。本品为一日1 次用药的口服片剂，须与其他支气管扩张药合用，适用于有频繁加重病史的成人患者慢性支气管炎相关严重COPD（舒张后FEV1 小于预计值的50%）的维持治疗。

[附件：http://focus-blog.pharmxplorer.at/2010/09/roflumilast-daxas%C2%AE-neuer-wirkstoff-zur-behandlung-der-copd/

Daxas (roflumilast) is a PDE4 inhibitor for use as an add-on to bronchodilator therapy in the maintenance of severe COPD.

PHARMACOLOGY

Roflumilast is a PDE4 inhibitor designed to target both the systemic and pulmonary inflammation associated with COPD. It acts by inhibiting PDE4, a major cyclic adenosine monophosphate (cAMP)-metabolising enzyme found in structural and inflammatory cells important to the pathogenesis of COPD. This inhibition results in reduced sputum neutrophils in patients with COPD. The major active metabolite, roflumilast N-oxide, acts in the same way.

CLINICAL STUDIES

Efficacy of roflumilast was assessed in two trials with identical design involving 3,091 adults with a history of severe to very severe COPD associated with chronic bronchitis and at least one exacerbation in the previous year.² Patients were randomised to receive roflumilast 500 microgram once a day or placebo, taken in the morning for 52 weeks. Patients were permitted to use long-acting β₂-agonists (LABAs) or short-acting anticholinergics during the studies plus short-acting β2-agonists as required; use of inhaled corticosteroids or theophylline was not allowed.

In a pooled analysis of the two studies, roflumilast was associated with an increase of 48ml in pre-bronchodilator FEV₁ compared with placebo (p<0.0001).² The rate (per patient per year) of moderate or severe exacerbations was 1.14 with roflumilast and 1.37 with placebo, corresponding to a relative risk reduction of 17 per cent.

The difference in exacerbation rates between treatments was independent of concomitant LABA use. The total number of exacerbations (excluding severe events) requiring treatment with systemic corticosteroids or antibiotics, or both, was also lower in the roflumilast group than in the placebo group.

Adverse events occurred in more patients in the roflumilast group than in the placebo group (67 per cent versus 62 per cent) and were associated with a greater rate of treatment discontinuation in the roflumilast group than in the placebo group (14 per cent versus 11 per cent).

Safety and efficacy of roflumilast were assessed in two double-blind, multicentre studies involving patients aged over 40 years with moderate to severe COPD who were randomly assigned to receive roflumilast 500 microgram or placebo once daily for 24 weeks in addition to either salmeterol (n=933) or tiotropium (n=743).³ Adherence to treatment was similar in all groups with mean compliance between 94 and 97 per cent.

Roflumilast was associated with a significant increase in mean pre-bronchodilator FEV₁ in both studies compared with placebo (49ml in the salmeterol study and 80ml in the tiotropium study). Similar improvements were noted in post-bronchodilator FEV₁ and in pre- and post-bronchodilator FVC. Roflumilast had a variable effect on symptomatic outcomes such as respiratory symptoms, use of rescue medications, and exacerbations in both trials.

The most frequently reported adverse events in both studies were COPD-related; the most common treatment-related adverse events were diarrhoea, nausea and weight loss, with no major differences between the two trials. The probability of treatment discontinuation in both studies was greater in patients receiving roflumilast.