近日，美国食品药品监督管理局（FDA）已批准青少年和成人哮喘患者使用AIRDUO RESPICLICK（丙酸氟替卡松吸入粉末）。该药物通过TEVA的Respiclick®呼吸激活多剂量干粉吸入器（MDPI）提供，该吸入器与TEVA呼吸产品组合中的其他批准药物一起使用。AIRDUO RESPICLICK是一种吸入性皮质类固醇（ICS），含有与氟利凡特相同的活性成分，用于维持治疗哮喘，作为12岁及12岁以上患者的预防性治疗。
批准日期：2017年1月30日 公司：Teva Pharmaceutical Industries Ltd.
AIRDUO RESPICLICK(丙酸氟替卡松和沙美特罗[fluticasone propionate and salmeterol])粉末吸入，55微克/14微克
AIRDUO RESPICLICK (丙酸氟替卡松和沙美特罗[fluticasone propionate and salmeterol])粉末吸入，113微克/14微克
AIRDUO RESPICLICK (丙酸氟替卡松和沙美特罗[fluticasone propionate and salmeterol])粉末吸入，232微克/14微克，
用于口腔吸入
美国初步批准:2000年
最近的重大变化
盒装警告——哮喘相关死亡——于2017年12月解除
适应症和用法:12/2017
警告和预防措施:12/2017
作用机制
AIRDUO RESPICLICK: AIRDUO RESPICLICK含有丙酸氟替卡松和沙美特罗。
下面描述的各个组件的作用机制适用于AIRDUO RESPICLICK。这些药物代表了两种不同类型的药物(一种合成皮质类固醇和一种LABA)，它们对临床、生理和炎症指标有不同的影响。
丙酸氟替卡松:丙酸氟替卡松是一种具有抗炎活性的合成三氟皮质激素。丙酸氟替卡松已在体外显示出对人糖皮质激素受体的结合亲和力，是地塞米松的18倍，几乎是倍氯米松-17单磷酸的两倍(BMP)是二丙酸倍氯米松的活性代谢物，是布地奈德的3倍以上。麦肯齐血管收缩试验在人类中的数据是一致的与这些结果。这些发现的临床意义尚不清楚。
炎症是哮喘发病机制的重要组成部分。皮质类固醇对多种细胞类型(如肥大细胞)有广泛的作用
炎症相关的细胞、嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞)和介质(如组胺、类二十烷酸、白三烯和细胞因子)。这些皮质激素的抗炎作用有助于哮喘的治疗。辛那福酸沙美特罗:沙美特罗是一种选择性LABA。体外研究表明，salmeterolto对β- 2肾上腺素受体的选择性至少是沙丁胺醇的50倍。虽然β- 2肾上腺素受体是支气管平滑肌中最主要的肾上腺素能受体，β- 1肾上腺素受体是心脏中最主要的受体，但人类心脏中也有β- 2肾上腺素受体，占总肾上腺素受体的10% - 50%。这些受体的确切功能尚未确定，但它们的存在增加了一种可能性，即即使是选择性的beta2激动剂也可能具有心功能。
beta2-adrenoceptor受体激动剂药物的药理作用,包括氟替卡松加沙美特罗,至少部分归因于刺激细胞内腺苷酸环化酶,theenzyme,催化三磷酸腺苷(ATP)的转换cyclic-3´, 5´一磷酸腺苷(环腺苷酸)。增加环AMP水平会导致支气管平滑肌松弛，抑制细胞，尤其是肥大细胞释放即刻过敏介质。
体外试验表明，沙美特罗是一种有效的、长期的肥大细胞介质释放抑制剂，如组胺、白三烯和前列腺素D2，从人的肺。沙美特罗抑制组胺诱导的血浆蛋白外溢，抑制血小板活化因子诱导的肺嗜酸性粒细胞积累。通过吸入途径给药的豚鼠。在人类中，通过吸入气溶胶给予单一剂量的沙美特罗可减轻过敏原引起的支气管反应，高反应性。
适应症和用法
AIRDUO RESPICLICK是一种含有皮质类固醇和LABA的固定剂量组合产品，用于:
•治疗12岁及以上患者的哮喘。
重要的使用限制:
•不适用于急性支气管痉挛的缓解。
剂量和管理
只适用于口腔吸入。
•初始剂量根据既往哮喘治疗和疾病严重程度而定。
•12岁及以上哮喘患者的治疗:1例吸入AIRDUORESPICLICK 55/14mcg, 113/14mcg，或232/14mcg，每日2次。
•不要与间隔器或容量保持室一起使用。
剂型和强度
吸入粉末含有氟替卡松丙酸55mcg, 113mcg，或232mcgand salmeterol(14mcg)每次驱动。
禁忌症
•哮喘状态或哮喘急性发作的初级治疗需要强化措施。
•对牛奶蛋白或AIRDUO RESPICLICK的任何成分极度过敏。
警告和预防措施
•LABA单药治疗会增加严重哮喘相关事件的风险。
•哮喘恶化和急性发作:不要用于缓解急性症状。在哮喘迅速恶化期间，患者需要立即重新评估。
•不要与含有LABA的其他药物联合使用，因为有过量使用的风险。
•局部感染:可能发生口腔和咽部白色念珠菌感染。
定期监测患者。建议患者吸入后用清水漱口，切勿吞咽，以减低风险。
•免疫抑制:现有结核病、真菌、细菌、病毒、寄生虫感染或眼部单纯疱疹的潜在恶化。小心使用于病人
这些感染。更严重甚至致命的水痘或麻疹病程可发生在易感患者。
•从全身皮质激素转移患者:从全身皮质激素转移时肾上腺功能受损的风险。逐渐从全身皮质类固醇如果转移到AIRDUO RESPICLICK。
•过敏和肾上腺抑制:在易感人群中，高剂量或正常剂量均可发生。如果发生这样的更改，请停止AIRDUO RESPICLICK缓慢。
•似是而非的支气管痉挛:如果发生似是而非的支气管痉挛，停止AIRDUO RESPICLICK并进行替代治疗。
•小心使用心血管或中枢神经系统疾病的患者，因为肾上腺素能刺激。
•骨密度降低:监测患者骨密度降低的主要危险因素。
•监测儿科患者的生长情况。
密切监测青光眼和白内障是必要的。
•警惕嗜酸性粒细胞、低钾血症和高血糖。
•惊厥性疾病、甲状腺毒症、糖尿病和酮症酸中毒患者慎用。
不良反应
最常见的不良反应包括鼻咽炎、口腔念珠菌病、背痛、头痛和咳嗽(报告的患者中超过或等于3%)。
报告可疑的不良反应，请联系Teva Respiratory, LLC at1-888-482-9522或FDA，电话1- 800-fdaa-1088或www.fda.gov/medwatch。
药物的相互作用
•强力细胞色素P450 3A4抑制剂(如利托那韦、酮康唑):不推荐使用。可能增加系统性皮质类固醇和心血管疾病的风险
效果。
•单胺氧化酶抑制剂和三环抗抑郁药:与极端使用。可能增强沙美特罗对血管系统的作用。
-受体阻滞剂:慎用。可阻断-受体激动剂的支气管扩张作用，引起严重的支气管痉挛。
利尿剂:慎用。与非保钾利尿剂相关的心电图改变和/或低钾血症可能伴随而恶化beta-agonists。
在特定人群中使用
•肝损害:监测全身皮质类固醇效应。
包装提供/储存和处理
提供
AIRDUO RESPICLICK作为一种白色干粉吸入器，有以下三种优点。每个吸入器都有一个黄色的盖子，分别用锡纸包装，纸盒里的袋子。每个吸入器含有0.45g的配方和提供60个驱动器:
强度NDC代码
AIRDUO 55/14 mcg NDC 59310-805-06
AIRDUO RESPICLICK 113/14 mcg NDC 59310-812-06
AIRDUO RESPICLICK 232/14 mcg NDC 59310-822-06
每个AIRDUO呼吸吸入器在执行器上都有一个剂量计数器。
病人不应该试图改变剂量计数器的数字。当计数器显示在打开箔袋后0、30天或之后丢弃吸入器
产品的到期日，以最先到期日为准。在计数器显示0后，甚至不能保证每个驱动器中的药物标签数量
虽然吸入器不是完全空的，将继续操作(见患者咨询信息)。
储存和处理
存储在室温(15°至25°C;59°、77°F)在干燥处;旅行允许从59°F到86°F (15°C到30°C)。避免暴露在极热、极冷或极潮湿的环境中。
请置于儿童接触不到的地方。
AIRDUO RESPICLICK应储存在未开封的防潮箔袋内，并在首次使用前立即从袋中取出。
打开锡箔袋30天后或柜台显示0时，以先到者为准。吸入器不可重复使用。不要试图把吸入器拆开
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AIRDUO RESPICLICK 113/14MCG INH 0.45GM  FLUTICASONE/SALMETEROL  TEVA PHARMACEUTICALS USA/BRAND NDC：59310081206
AIRDUO RESPICLICK 232/14MCG INH 0.45GM FLUTICASONE/SALMETEROL  TEVA PHARMACEUTICALS USA/BRAND NDC：59310082206
AIRDUO RESPICLICK 55/14MCG INH 0.45GM FLUTICASONE/SALMETEROL  TEVA PHARMACEUTICALS USA/BRAND NDC：59310080506
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AirDuo RespiClick(fluticasone propionate/salmeterol)
IMPORTANT SAFETY INFORMATION
Contraindications: AirDuo RespiClick is contraindicated in:
Primary treatment of status asthmaticus or other acute episodes of asthma requiring intensive measures
Patients with known severe hypersensitivity to milk proteins or any ingredients of AirDuo RespiClick
Serious Asthma-Related Events—Hospitalizations, Intubations, Death: Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone
Deterioration of Disease and Acute Episodes: AirDuo RespiClick should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma. AirDuo RespiClick is not indicated for the relief of acute bronchospasm. An inhaled, short-acting beta2-agonist, not AirDuo RespiClick, should be used to relieve acute symptoms such as shortness of breath
Excessive Use and Use with Other Long acting Beta2-Agonists: AirDuo RespiClick should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using AirDuo RespiClick should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason
Local Effects of ICS: Oropharyngeal candidiasis has occurred in patients treated with AirDuo RespiClick. Advise patients to rinse the mouth with water without swallowing following inhalation
Immunosuppression: Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use with caution in patients with the above because of the potential for worsening of these infections
Transferring Patients from Systemic Corticosteroid Therapy: Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS. Taper patients slowly from systemic corticosteroids if transferring to AirDuo RespiClick
Hypercorticism and Adrenal Suppression may occur with high doses of ICS, including fluticasone propionate, or at the recommended dose in susceptible individuals. If such changes occur, discontinue AirDuo RespiClick slowly
Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors: The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, ketoconazole) with AirDuo RespiClick is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur
Paradoxical Bronchospasm and Upper Airway Symptoms: If paradoxical bronchospasm occurs, discontinue AirDuo RespiClick immediately and institute alternative therapy
Hypersensitivity Reactions, Including Anaphylaxis: Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of AirDuo RespiClick. Discontinue AirDuo RespiClick if such reactions occur
Cardiovascular and Central Nervous System Effects: Salmeterol, a component of AirDuo RespiClick, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. If such effects occur, AirDuo RespiClick may need to be discontinued. AirDuo RespiClick should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
Reduction in Bone Mineral Density (BMD): Decreases in BMD have been observed with long-term administration of products containing ICS. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care
Effect on Growth: ICS, as well as poorly controlled asthma, may cause a reduction in growth velocity, and the long-term effect on final adult height is unknown. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma. Monitor growth of pediatric patients
Glaucoma and Cataracts: Long-term use of ICS, including fluticasone propionate, a component of AirDuo RespiClick, may increase the risk for cataracts or glaucoma. Regular eye exams should be considered
Eosinophilic Conditions and Churg-Strauss Syndrome: Systemic eosinophilic conditions, such as Churg-Strauss syndrome, may occur. Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy
Coexisting Conditions: Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
Hypokalemia and Hyperglycemia: Be alert to hypokalemia and hyperglycemia
Adverse Reactions: Most common adverse reactions (≥3%) in patients taking AirDuo RespiClick 55/14 mcg twice daily, 113/14 mcg twice daily, 232/14 mcg twice daily, and placebo, respectively, were nasopharyngitis (8.6%, 4.8%, 6.9%, 4.4%), oral candidiasis (1.6%, 2.2%, 3.4%, 0.7%), back pain (3.1%, 0.7%, 0%, 1.8%), headache (5.5%, 4.8%, 2.8%, 4.4%), and cough (2.3%, 3.7%, 0.7%, 2.6%)
1：http://hcp.myairduo.com/Assets/Pdf/PI.pdf
2：http://hcp.myairduo.com/Assets/Pdf/PI.pdf