芜地溴铵-维兰特罗粉吸入剂 ANORO ELLIPTA (umeclidinium and vilanterol) FDA药品说明书翻译.pdf

FULL PRESCRIBING INFORMATION WARNING ASTHMA RELATED DEATH 警告 哮喘相关死亡警告 哮喘相关死亡 Long acting beta2 adrenergic agonists LABA increase the risk of asthma related death Data from a large placebo controlled US trial that compared the safety of another LABA salmeterol with placebo added to usual asthma therapy showed an increase in asthma related deaths in subjects receiving salmeterol This finding with salmeterol is considered a class effect of all LABA including vilanterol one of the active ingredients in ANORO ELLIPTA see Warnings and Precautions 5 1 长效 2 肾上腺素受体激动药 LABA 可增加哮喘相关死亡的风险 美国一项大型安慰 剂对照临床试验数据显示 与安慰剂相比 将另一种LABA沙美特罗加入常规哮喘治疗方 案中 接受沙美特罗的受试者出现哮喘相关死亡的风险增加 所有LABA应都具有沙美特 罗的这种类似作用 包括本药活性成分之一维兰特罗 The safety and efficacy of ANORO ELLIPTA in patients with asthma have not been established ANORO ELLIPTA is not indicated for the treatment of asthma 本药用于哮喘患者的安全性和有效性尚不明确 本药不适用于治疗哮喘 1 INDICATIONS AND USAGE 适应症和用适应症和用途途 ANORO ELLIPTA is a combination anticholinergic long acting beta2 adrenergic agonist anticholinergic LABA indicated for the long term once daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease COPD including chronic bronchitis and or emphysema 本药为抗胆碱能药和LABA的复方制剂 用于慢性阻塞性肺疾病 COPD 包括慢性支气 管炎和 或 肺气肿 患者气道阻塞的长期维持治疗 Important Limitations of Use ANORO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma 重要使用限制 本药不适用于缓解急性支气管痉挛或治疗哮喘 2 DOSAGE AND ADMINISTRATION 用法用量用法用量 ANORO ELLIPTA umeclidinium vilanterol 62 5 mcg 25 mcg should be administered as 1 inhalation once daily by the orally inhaled route only 本药仅用于口腔吸入 一次1吸 芜地溴铵62 5 g 维兰特罗25 g 一日1次 ANORO ELLIPTA should be taken at the same time every day Do not use ANORO ELLIPTA more than 1 time every 24 hours 每日同一时刻给药 24小时用药不超过1次 No dosage adjustment is required for geriatric patients patients with renal impairment or patients with moderate hepatic impairment see Clinical Pharmacology 12 3 老年人 肾功能损害者 中度肝功能损害者无需调整用药剂量 3 DOSAGE FORMS AND STRENGTHS 剂型和规格剂型和规格 Inhalation Powder Disposable light grey and red plastic inhaler containing 2 double foil blister strips each with 30 blisters containing powder intended for oral inhalation only One strip contains umeclidinium 62 5 mcg per blister and the other strip contains vilanterol 25 mcg per blister An institutional pack containing 7 blisters per strip is also available 芜地溴铵 维兰特罗粉吸入剂 每吸含芜地溴铵62 5 g 维兰特罗25 g 4 CONTRAINDICATIONS 禁忌症禁忌症 The use of ANORO ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to umeclidinium vilanterol or any of the excipients see Warnings and Precautions 5 6 Description 11 1 对芜地溴铵 维兰特罗过敏者 2 对牛奶蛋白严重过敏者 5 WARNINGS AND PRECAUTIONS 警告和注意事项警告和注意事项 5 1 Asthma Related Death 哮喘相关死亡哮喘相关死亡 Data from a large placebo controlled trial in subjects with asthma showed that LABA may increase the risk of asthma related death Data are not available to determine whether the rate of death in patients with COPD is increased by LABA 一项大型安慰剂对照临床试验数据显示 LABA可增加哮喘相关死亡的风险 数据尚不 足以确定COPD患者使用LABA死亡率是否增加 A 28 week placebo controlled US trial comparing the safety of another LABA salmeterol with placebo each added to usual asthma therapy showed an increase in asthma related deaths in subjects receiving salmeterol 13 13 176 in subjects treated with salmeterol vs 3 13 179 in subjects treated with placebo relative risk 4 37 95 CI 1 25 15 34 The increased risk of asthma related death is considered a class effect of LABA including vilanterol one of the active ingredients in ANORO ELLIPTA 美国一项28周 安慰剂对照临床试验数据显示 与安慰剂相比 将另一种LABA沙美特 罗加入常规哮喘治疗方案中 接受沙美特罗的受试者出现哮喘相关死亡的风险增加 沙美特 罗组13 13 176 安慰剂组3 13 179 所有LABA应都具有沙美特罗的这种类似作用 包括本 药活性成分之一维兰特罗 No trial adequate to determine whether the rate of asthma related death is increased in subjects treated with ANORO ELLIPTA has been conducted The safety and efficacy of ANORO ELLIPTA in patients with asthma have not been established ANORO ELLIPTA is not indicated for the treatment of asthma 尚无充足的试验以确定COPD患者使用本药哮喘相关死亡率是否增加 本药用于哮喘患 者的安全性和有效性尚不明确 本药不适用于治疗哮喘 5 2 Deterioration of Disease and Acute Episodes 症状恶化和急性发作症状恶化和急性发作 ANORO ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life threatening episodes of COPD ANORO ELLIPTA has not been studied in subjects with acutely deteriorating COPD The initiation of ANORO ELLIPTA in this setting is not appropriate COPD迅速恶化或患者出现可能危及生命的发作时不得使用本药 尚无COPD迅速恶化 患者用药的研究 本药不适用于此类患者 ANORO ELLIPTA should not be used for the relief of acute symptoms i e as rescue therapy for the treatment of acute episodes of bronchospasm ANORO ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose Acute symptoms should be treated with an inhaled short acting beta2 agonist 本药不用于缓解急性症状 如作为支气管痉挛急性发作的救援治疗 尚无本药用于缓解 急性症状的研究 不得使用超出剂量以缓解急性症状 如出现急性症状应使用吸入型 短效 2 肾上腺素受体激动药治疗 When beginning treatment with ANORO ELLIPTA patients who have been taking oral or inhaled short acting beta2 agonists on a regular basis e g 4 times a day should be instructed to discontinue the regular use of these drugs and to use them only for symptomatic relief of acute respiratory symptoms When prescribing ANORO ELLIPTA the healthcare provider should also prescribe an inhaled short acting beta2 agonist and instruct the patient on how it should be used Increasing inhaled short acting beta2 agonist use is a signal of deteriorating disease for which prompt medical attention is indicated 定期 如一日4次 使用口服或吸入型短效 2 肾上腺素受体激动药的患者如开始使用本药 应停用之前的药物 仅在需要缓解急性呼吸系统症状时方可使用 当开具本药时 医生应同 时开具一种吸入型 短效 2 肾上腺素受体激动药并指导患者如何用药 患者需要更大剂量 的吸入型 短效 2 肾上腺素受体激动药 可能意味着疾病正在恶化 需注意 COPD may deteriorate acutely over a period of hours or chronically over several days or longer If ANORO ELLIPTA no longer controls symptoms of bronchoconstriction the patient s inhaled short acting beta2 agonist becomes less effective or the patient needs more short acting beta2 agonist than usual these may be markers of deterioration of disease In this setting a re evaluation of the patient and the COPD treatment regimen should be undertaken at once Increasing the daily dose of ANORO ELLIPTA beyond the recommended dose is not appropriate in this situation COPD可能在数小时内迅速恶化 也可在数日内缓慢恶化 如本药已不可控制支气管狭 窄症状 或患者使用的吸入型 短效 2 肾上腺素受体激动药开始失效 或患者需要更大剂 量的短效 2 肾上腺素受体激动药 可能意味着疾病正在恶化 此时需立即对患者重新评估 并开始COPD治疗 此时不适于将本药剂量增加至超过推荐剂量 5 3 Excessive Use of ANORO ELLIPTA and Use With Other Long Acting Beta2Agonists 过过 量使用本药和与其他量使用本药和与其他LABA合用合用 ANORO ELLIPTA 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 ANORO ELLIPTA should not use another medicine containing a LABA e g salmeterol formoterol fumarate arformoterol tartrate indacaterol for any reason 本药不得超过推荐用药间隔经常使用 或超出推荐剂量使用 本药亦不得与其他含 LABA的药物合用 已有与过度使用吸入型抗胆碱能药相关的药物过量可导致临床显著的心 血管不良反应和死亡的报道 使用本药患者不得因任何原因使用其他含LABA的药物 如沙 美特罗 富马酸福莫特罗 酒石酸阿福特罗 茚达特罗 5 4 Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors 与与强效细胞色素强效细胞色素 P450 CYP 3A4抑制药的相互作用抑制药的相互作用 Caution should be exercised when considering the coadministration of ANORO ELLIPTA with long term ketoconazole and other known strong cytochrome P450 3A4 CYP3A4 inhibitors e g ritonavir clarithromycin conivaptan indinavir itraconazole lopinavir nefazodone nelfinavir saquinavir telithromycin troleandomycin voriconazole because increased cardiovascular adverse effects may occur see Drug Interactions 7 1 Clinical Pharmacology 12 3 本药与强效CYP 3A4抑制药 如长期使用酮康唑 利托那韦 克拉霉素 考尼伐坦 茚 地那韦 伊曲康唑 洛匹那韦 奈法唑酮 奈非那韦 沙奎那韦 泰利霉素 醋竹桃霉素 伏立康唑 合用应谨慎 合用可导致心血管不良反应增加 5 5 Paradoxical Bronchospasm 矛盾性支气管痉挛矛盾性支气管痉挛 As with other inhaled medicines ANORO ELLIPTA can produce paradoxical bronchospasm which may be life threatening If paradoxical bronchospasm occurs following dosing with ANORO ELLIPTA it should be treated immediately with an inhaled short acting bronchodilator ANORO ELLIPTA should be discontinued immediately and alternative therapy should be instituted 本药与其他吸入型药物合用时可出现危及生命的矛盾性支气管痉挛 如出现 应立即停 药 使用吸入型 短效支气管扩张药治疗 并采用替代疗法 5 6 Hypersensitivity Reactions 过敏反应过敏反应 Hypersensitivity reactions may occur after administration of ANORO ELLIPTA There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose therefore patients with severe milk protein allergy should not use ANORO ELLIPTA see Contraindications 4 使用本药可出现过敏反应 已有对牛奶蛋白严重过敏者吸入其他含乳糖产品出现过敏反 应的报道 故对牛奶蛋白严重过敏者不得使用本药 5 7 Cardiovascular Effects 心血管不良反应心血管不良反应 Vilanterol like other beta2 agonists can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate systolic or diastolic blood pressure or symptoms see Clinical Pharmacology 12 2 If such effects occur ANORO ELLIPTA may need to be discontinued In addition beta agonists have been reported to produce electrocardiographic changes such as flattening of the T wave prolongation of the QTc interval and ST segment depression although the clinical significance of these findings is unknown 与其他 2 肾上腺素受体激动药相似 维兰特罗可引起部分患者出现临床显著的心血管 不良反应 测定表现为为脉搏率 心脏收缩压或舒张压增加 或症状加重 如出现以上不良 反应 应停用本药 另外 受体激动药有引起心电图改变 如T波扁平 QT间期延长 ST 段下移 的报道 但其临床意义尚不明确 Therefore ANORO ELLIPTA should be used with caution in patients with cardiovascular disorders especially coronary insufficiency cardiac arrhythmias and hypertension 心血管疾病 尤其冠状动脉功能不全 心律失常 高血压 患者使用本药应谨慎 5 8 Coexisting Conditions 共存条件共存条件 ANORO ELLIPTA like all medicines containing sympathomimetic amines should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines Doses of the related beta2 adrenoceptor agonist albuterol when administered intravenously have been reported to aggravate preexisting diabetes mellitus and ketoacidosis 与所有拟交感类药物相似 本药慎用于抽搐疾病或甲状腺功能亢进患者 以及常对拟交 感类药物有反应者 静脉给予 2 肾上腺素受体激动药沙丁胺醇剂量时 有加重已有糖尿病 和酮酸中毒的报道 5 9 Worsening of Narrow Angle Glaucoma 狭角性青狭角性青光眼加重光眼加重 ANORO ELLIPTA should be used with caution in patients with narrow angle glaucoma Prescribers and patients should be alert for signs and symptoms of acute narrow angle glaucoma e g eye pain or discomfort blurred vision visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema Instruct patients to consult a physician immediately should any of these signs or symptoms develop 狭角性青光眼患者使用本药应谨慎 医生及患者应警觉急性狭角性青光眼的迹象和症状 如眼痛 眼部不适 视物模糊 视物光晕 与结膜充血引起红眼相关的有色影像 角膜水 肿 如出现以上迹象或症状加重 患者应立即求医 5 10 Worsening of Urinary Retention 尿潴留加重尿潴留加重 ANORO ELLIPTA should be used with caution in patients with urinary retention Prescribers and patients should be alert for signs and symptoms of urinary retention e g difficulty passing urine painful urination especially in patients with prostatic hyperplasia or bladder neck obstruction Instruct patients to consult a physician immediately should any of these signs or symptoms develop 尿潴留患者使用本药应谨慎 医生及患者应警觉尿潴留的迹象和症状 如排尿困难 排 尿疼痛 尤其前列腺增生或膀胱颈阻塞患者 如出现以上任一迹象或症状加重 患者应立 即求医 5 11 Hypokalemia and Hyperglycemia 低钾血症和高糖血症低钾血症和高糖血症 Beta adrenergic agonist medicines may produce significant hypokalemia in some patients possibly through intracellular shunting which has the potential to produce adverse cardiovascular effects The decrease in serum potassium is usually transient not requiring supplementation Beta agonist medicines may produce transient hyperglycemia in some patients In 4 clinical trials of 6 month duration evaluating ANORO ELLIPTA in subjects with COPD there was no evidence of a treatment effect on serum glucose or potassium 肾上腺素受体激动药可引起部分患者出现显著的低钾血症 可能通过细胞通路 有引 起心血管不良反应的潜在可能 血清钾浓度降低常为短暂性 无需使用补充剂 肾上腺素 受体激动药可引起部分患者出现短暂的高糖血症 在4项为期6个月时间的评估性临床试验中 本药用于COPD患者 未显示本药对血糖或钾有治疗作用的证据 6 ADVERSE REACTIONS 不良反应不良反应 LABA such as vilanterol one of the active ingredients in ANORO ELLIPTA increase the risk of asthma related death ANORO ELLIPTA is not indicated for the treatment of asthma See Boxed Warning and Warnings and Precautions 5 1 LABA 如本药活性成分之一维兰特罗 增加哮喘相关死亡的风险 本药不适用于治疗 哮喘 The following adverse reactions are described in greater detail in other sections 下列不良反 应已在说明书其他章节讨论 Paradoxical bronchospasm see Warnings and Precautions 5 5 Cardiovascular effects see Warnings and Precautions 5 7 Worsening of narrow angle glaucoma see Warnings and Precautions 5 9 Worsening of urinary retention see Warnings and Precautions 5 10 矛盾性支气管炎 心血管不良反应 狭角性青光眼加重 尿潴留加重 6 1 Clinical Trials Experience 临床试验经验临床试验经验 Because clinical trials are conducted under widely varying conditions adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice 由于临床试验是在各种不同条件下进行的 观察到的不良反应发生率不能直接与其他 临床试验中的发生率相比较 可能也不能反应临床实践中观察到的发生率 The clinical program for ANORO ELLIPTA included 8 138 subjects with COPD in four 6 month lung function trials one 12 month long term safety study and 9 other trials of shorter duration A total of 1 124 subjects have received at least 1 dose of ANORO ELLIPTA umeclidinium vilanterol 62 5 mcg 25 mcg and 1 330 subjects have received a higher dose of umeclidinium vilanterol 125 mcg 25 mcg The safety data described below are based on the four 6 month and the one 12 month trials Adverse reactions observed in the other trials were similar to those observed in the confirmatory trials 本药临床试验项目共包括8138名COPD受试者 参与4项目为期6个月的肺功能试验 1项为期12个月的长期安全性研究 以及9项其他短期试验 共计1124名受试者接受至少1 次剂量的本药 芜地溴铵62 5 g 维兰特罗25 g 1330名受试者接受更高剂量本药 芜地溴 铵125 g 维兰特罗25 g 以下安全性数据基于4项为期6个月的临床试验以及1项为期12 个月的临床试验结果 在其他临床试验中观察到的不良反应与验证性临床试验结果相似 6 Month Trials The incidence of adverse reactions associated with ANORO ELLIPTA in Table 1 is based on four 6 month trials 2 placebo controlled trials Trials 1 and 2 n 1 532 and n 1 489 respectively and 2 active controlled trials Trials 3 and 4 n 843 and n 869 respectively Of the 4 733 subjects 68 were male and 84 were Caucasian They had a mean age of 63 years and an average smoking history of 45 pack years with 50 identified as current smokers At screening the mean post bronchodilator percent predicted forced expiratory volume in 1 second FEV1 was 48 range 13 to 76 the mean post bronchodilator FEV1 forced vital capacity FVC ratio was 0 47 range 0 13 to 0 78 and the mean percent reversibility was 14 range 45 to 109 6个月临床试验 表1中与本药相关的不良反应发生率数据基于4项为期6个月的临床试 验 包括2项安慰剂对照试验 试验1 试验2 2项活性对照试验 试验3 试验4 共4733 名受试者 其中68 为男性 84 为白种人 平均年龄63岁 平均吸烟数值为45pack years 50 为正在吸烟者 经检查 使用支气管扩张药后预测的第一秒用力呼气量 FEV1 平均值为 48 范围13 76 使用支气管扩张药后FEV1 用力肺活量 FVC 平均比值为0 47 范围 0 13 0 78 可逆性百分比平均值为14 45 109 Subjects received 1 dose once daily of the following ANORO ELLIPTA umeclidinium vilanterol 125 mcg 25 mcg umeclidinium 62 5 mcg umeclidinium 125 mcg vilanterol 25 mcg active control or placebo 受试者接受每日1次的以下剂量本药 芜地溴铵125 g 维兰特罗25 g 芜地溴 铵62 5 g 芜地溴铵125 g 维兰特罗25 g 活性对照或安慰剂 Table 1 Adverse Reactions With ANORO ELLIPTA With 1 Incidence and More Common Than With Placebo in Subjects With Chronic Obstructive Pulmonary Disease 表表 1 COPD 受试者中本药较安慰剂更为常见发生程度 且发生率受试者中本药较安慰剂更为常见发生程度 且发生率 1 的不良反应的不良反应 Adverse Reaction 不良反应 Placebo n 555 安慰剂 组 ANORO ELLIPTA n 842 本药组 Umeclidiniu m 62 5 mcg n 418 芜地溴铵 62 5 g Vilanterol 25 mcg n 1 034 维兰特罗 25 g Infections and infestations感染性疾病 Pharyngitis 咽炎 Sinusitis 鼻窦炎 Lower respiratory tract 下呼吸道感染 Infection 感染 1 1 1 2 1 1 1 1 1 2 1 1 Gastrointestinal disorders 胃肠道不适 Constipation 便秘 1 1 1 1 Diarrhea 腹泻 1 2 1 2 Musculoskeletal and connective tissue disorders 肌肉骨骼和结缔组织疾病 Pain in extremity 四肢疼痛 Muscle spasms 肌肉痉挛 Neck pain 颈痛 1 1 1 2 1 1 1 1 1 2 1 1 General disorders and administration site conditions 一般疾病 Chest pain 胸痛 1 1 1 1 Other adverse reactions with ANORO ELLIPTA observed with an incidence less than 1 but more common than with placebo included the following productive cough dry mouth dyspepsia abdominal pain gastroesophageal reflux disease vomiting musculoskeletal chest pain chest discomfort asthenia atrial fibrillation ventricular extrasystoles supraventricular extrasystoles myocardial infarction pruritus rash and conjunctivitis 其他本药较安慰剂更为常见发生程度 且发生率 1 的不良反应包括 排痰性咳嗽 口干 消化不良 上腹部疼痛 胃食管反流疾病 呕吐 肌肉骨骼胸痛 胸部不适 乏力 心房颤动 室性早搏 室上性期外收缩 心肌梗死 瘙痒 皮疹 结膜炎 12 Month Trial In a long term safety trial 335 subjects were treated for up to 12 months with umeclidinium vilanterol 125 mcg 25 mcg or placebo The demographic and baseline characteristics of the long term safety trial were similar to those of the placebo controlled efficacy trials described above Adverse reactions that occurred with a frequency of greater than or equal to 1 in the group receiving umeclidinium vilanterol 125 mcg 25 mcg that exceeded that in placebo in this trial were headache back pain sinusitis cough urinary tract infection arthralgia nausea vertigo abdominal pain pleuritic pain viral respiratory tract infection toothache and diabetes mellitus 12个月临床试验 在一项长期安全性临床试验中 335名受试者接受芜地溴铵125 g 维兰特罗25 g或安慰剂治疗12个月 这项长期安全性临床试验的人口统计和基线特征与 上述安慰剂对照有效性试验相似 在这项试验中 本药 芜地溴铵125 g 维兰特罗25 g 较安慰剂更为常见发生程度 且发生率 1 的不良反应包括 头痛 背痛 鼻窦炎 咳 嗽 尿道感染 关节痛 恶心 眩晕 上腹疼痛 胸膜痛 病毒性呼吸道感染 牙痛 糖尿病 7 DRUG INTERACTIONS 药物相互作用药物相互作用 7 1 Inhibitors of Cytochrome P450 3A4 CYP 3A4抑制药抑制药 Vilanterol a component of ANORO ELLIPTA is a substrate of CYP3A4 Concomitant administration of the strong CYP3A4 inhibitor ketoconazole increases the systemic exposure to vilanterol Caution should be exercised when considering the coadministration of ANORO ELLIPTA with ketoconazole and other known strong CYP3A4 inhibitors e g ritonavir clarithromycin conivaptan indinavir itraconazole lopinavir nefazodone nelfinavir saquinavir telithromycin troleandomycin voriconazole see Warnings and Precautions 5 4 Clinical Pharmacology 12 3 本药成分之一维兰特罗为CYP 3A4底物 本药与强效CYP 3A4抑制药酮康唑合用增加维 兰特罗的系统暴露量 本药与酮康唑和其他已知的强效CYP 3A4抑制药 如利托那韦 克拉 霉素 考尼伐坦 茚地那韦 伊曲康唑 洛匹那韦 奈法唑酮 奈非那韦 沙奎那韦 泰利 霉素 醋竹桃霉素 伏立康唑 合用应谨