近日，美国食品和药品监督管理局(FDA)批准Daliresp(roflumilast)，每天服用一药丸减低来自严重慢性阻塞性肺疾病(COPD)频繁发作(加重)或症状的恶化。
Roflumilast，治疗COPD 新药类别，是一种被称为4型磷酸二酯酶(PDE-4)酶的抑制剂。适用于有严重COPD人们治疗咳嗽症状和与支气管炎关联的多量粘液。Roflumilast不意向治疗主要肺气肿的另一种形式COPD。
FDA的药物评价和研究中心中药物评价II部主任Curtis Rosebraugh, M.D., M.P.H说“COPD是一种随时间变坏的严重疾病，”“新的治疗选择减低发作或加重频数在帮助有COPD伴慢性支气管炎和加重史患者处理这种使人衰弱疾病是很重要的。
处方修改批准：2018年1月30日；公司：阿斯利康
DALIRESP(罗氟司特[roflumilast])片,供口服使用
美国初步批准：2011年
近期重大变化
剂量和给药：2018年1月
警告和预防措施，精神病
自杀事件：2017年8月
作用机理
罗氟胺及其活性代谢物（罗氟胺N-氧化物）是磷酸二酯酶4（PDE4）的选择性抑制剂。rofluminast和rofluminast n-oxide抑制pde4（肺组织中一种主要的环-3′，5′-磷酸腺苷（环AMP）-代谢酶）的活性导致细胞内环AMP的积累。虽然daliresp对慢性阻塞性肺病患者的治疗作用的具体机制尚不明确，但它被认为与肺细胞内循环AMP增加的作用有关。
适应症和使用
Daliresp是一种选择性磷酸二酯酶4抑制剂，用于降低慢性支气管炎伴严重慢性阻塞性肺病患者的慢性阻塞性肺病恶化风险和有恶化史的治疗。
使用限制：
•Daliresp不是支气管扩张剂，不用于缓解急性支气管痉挛。
•daliresp 250mcg是一种起始剂量，仅在治疗的前4周，不是有效（治疗）剂量。
剂量和给药
慢性阻塞性肺病患者的维持剂量为每天一片500mcg药片，不论是否有食物。在4周内，每天开始一次剂量为250mcg的DaliResp治疗，此后每天增加一次剂量为500mcg，可能会降低一些患者的治疗中止率。
剂型及强度
片剂：250毫克、500毫克
禁忌症
中度到重度肝损伤（儿童Pugh B或C）
警告和注意事项
•急性支气管痉挛：不要用于缓解急性支气管痉挛。
•包括自杀在内的精神事件：建议患者、其护理者和家庭警惕失眠、焦虑、抑郁、自杀想法或其他情绪变化的出现或恶化，如果发生此类变化，请联系医疗保健提供者。在有抑郁症和/或自杀想法或行为史的患者中，仔细权衡用达利思普治疗的风险和益处。
•减肥：定期监测体重。如果出现不明原因或临床意义重大的体重减轻，评估体重减轻，并考虑停用达利思普。
•药物相互作用：不建议与强细胞色素P450酶诱导剂（如利福平、苯巴比妥、卡马西平、苯妥英钠）一起使用。
不良反应
最常见的不良反应（≥2%）是腹泻、体重减轻、恶心、头痛、背痛、流感、失眠、头晕和食欲下降。
要报告可疑的不良反应，请致电1-800-236-9933联系阿斯利康或致电1-800-FDA-1088联系FDA或www.fda.gov/medwatch。
药物相互作用
与cyp3a4抑制剂或cyp3a4和cyp1a2双重抑制剂（如红霉素、酮康唑、氟伏沙明、依诺沙星、西米替丁）一起使用会增加罗氟明的全身暴露，并可能导致不良反应增加。这种同时使用的风险应与利益进行仔细权衡。
在特定人群中使用
哺乳期母亲：哺乳期妇女不应使用DaliResp，因为可能会将Rofluminast和/或其代谢物排泄到母乳中，而且没有人类研究调查DaliResp对母乳喂养婴儿的影响。
包装供应/储存和搬运
供应
DALIRESP 500MCG TAB 20 UD  ROFLUMILAST  ASTRA ZENECA PHARM  NDC：310009539
DALIRESP 250MCG TAB 20  ROFLUMILAST  ASTRA ZENECA PHARM  NDC：310008839
DALIRESP 250MCG TAB 28  ROFLUMILAST  ASTRA ZENECA PHARM  NDC：310008828
DALIRESP 500MCG TAB 30  ROFLUMILAST  ASTRA ZENECA PHARM  NDC：310009530
DALIRESP 500MCG TAB 90  ROFLUMILAST  ASTRA ZENECA PHARM  NDC：310009590
储存和搬运
在20°C-25°C（68°F-77°F）下储存Daliresp片剂；允许偏离15°C-30°C（59°F-86°F）。[见USP控制的室温]。
完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9a1d0a8-581f-4f91-a2b8-f419192d0ebf 
COPD therapy now available in pill form
COPD therapy now available in pill form Product: Daliresp
Company: Forest
Pharmacologic class: Selective phosphodiesterase 4 (PDE4) inhibitor.
Active ingredient: Roflumilast 500 μg; tabs.
Indication: To reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations in severe COPD patients with chronic bronchitis and a history of exacerbations. Not for the relief of acute bronchospasm.
Pharmacology: Both roflumilast and its active metabolite (roflumilast N-oxide) selectively inhibit the activity of PDE4, an enzyme that mediates the breakdown of intracellular cyclic adenosine monophosphate (AMP). The resultant increased levels of intracellular cyclic AMP in lung cells may be related to the clinical effects of roflumilast, but the exact mechanism of action is not well defined.
Clinical trials: The safety and efficacy of roflumilast in the management of COPD was eva luated in several randomized, double-blind, controlled, parallel group clinical trials involving a total of 9,394 adult patients with nonreversible obstructive lung disease.
Four of these were placebo-controlled one-year trials in patients with severe COPD that were designed to eva luate the efficacy of roflumilast on COPD exacerbations. In two of these trials, inhaled corticosteroids and short-acting beta agonists were allowed. Lung function (FEV1) and the rate of moderate or severe COPD exacerbations was a co-primary endpoint. Both trials failed to show a significant reduction in the rate of COPD exacerbations.
Subsequent trials were designed based on an analysis of a subset of these patients who appeared to have a better response compared to the overall population. These two trials enrolled 3,096 patients with severe COPD associated with chronic bronchitis, at least one COPD exacerbation in the previous year, and at least a 20 pack-year smoking history.
Long-acting beta agonists and short-acting anti-muscarinics were allowed, but not inhaled corticosteroids. In both of these trials, roflumilast 500 μg once daily showed a significant reduction in the rate of moderate or severe COPD exacerbations compared to placebo. Also, in these four trials, roflumilast 500 μg daily resulted in a significant improvement in lung function.
Two additional studies were six-month efficacy trials in patients with moderate-to-severe COPD conducted to assess the effect on lung function of roflumilast as add-on therapy to a long-acting beta agonist or a long-acting anti-muscarinic. No trials have been conducted to assess the effects of roflumilast on COPD exacerbations when added to a fixed-dose combination product containing a long-acting beta agonist and inhaled corticosteroid.
Adults: 500 μg once daily.
Children: Not recommended.
Contraindications: Moderate-to-severe liver impairment.
Warnings/Precautions: Depression. Suicidal ideation. Mild liver impairment (Child-Pugh Class A). Monitor for insomnia, anxiety, depression, suicidal ideation, other mood changes; reeva luate if occurs. Monitor weight regularly; consider discontinuing if unexplained or significant weight loss occurs. Pregnancy (Cat. C). Labor & delivery, nursing mothers: not recommended.
Interactions: Concomitant strong CYP450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin): not recommended. Potentiated by CYP3A4 and CYP1A2 inhibitors (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine), and by oral contraceptives containing gestodene + ethinyl estradiol (possible increased adverse effects).
Adverse reactions: GI upset, weight decrease, headache, back pain, influenza, dizziness, decreased appetite; psychiatric effects.
How supplied: Tabs — 30 
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附件:
20117621522015.PDF