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Ofev Capsules（Nintedanib Ethanesulfonate）尼达尼布胶囊

2015-09-05 02:34:04 作者：新特药房来源：互联网浏览次数：28 文字大小：【大】【中】【小】

简介： Ofev Capsules（Nintedanib Ethanesulfonate）为一种阻断多路径的激酶抑制剂，所述路径可能包括肺组织的瘢痕化。其安全性与有效性在包含1231名患有IPF的患者的三个临床试验中得到确定。服用Ofev的患者与 ...

关键字：Nintedanib Ethanesulfonate商品名Ofev Capsules 突破性治疗特发性肺纤维化孤儿药物快速通道优先审评

Ofev Capsules（Nintedanib Ethanesulfonate）为一种阻断多路径的激酶抑制剂，所述路径可能包括肺组织的瘢痕化。其安全性与有效性在包含1231名患有IPF的患者的三个临床试验中得到确定。服用Ofev的患者与服用安慰剂的患者相比，用力肺活量(即尽最大力深呼吸后用力从肺中呼出的空气的量)衰退的现象得到显著的减少。
批准日期：2014年10月15日；公司：勃林格殷格翰制药公司
OFEV(nintedanib)胶囊，为口服使用
初次批准：2014
适应证和用途
OFEV是一种激酶抑制剂适用为特发性肺纤维化(IPF)的治疗。
剂量和给药方法
⑴ 推荐剂量：150mg每天2次间隔约12小时与食物服用。
⑵ 考虑暂时剂量减低至100mg，治疗中断，或终止为处理不良反应。
⑶ 治疗前，进行肝功能检验。
剂型和规格
胶囊：150mg和100mg
禁忌证
无
警告和注意事项
⑴ 肝酶升高：用OFEV曾发生ALT，AST，和胆红素升高。治疗前和期间监视ALT，AST，和胆红素。可能需要暂时减低剂量或终止。
⑵ 胃肠道疾病：用OFEV曾发生腹泻，恶心，和呕吐。第一个征象用充分水化和止泻药(如，洛哌丁胺[loperamide])或抗吐药治疗患者。如尽管对症治疗严重腹泻，恶心，或呕吐持续终止OFEV。
⑶ 胚胎胎儿毒性：应劝告育龄妇女对胎儿潜在危害和避免成为妊娠。
⑷ 曾报道动脉血栓栓塞事件。当治疗患者处于较高心血管风险包括已知冠状动脉疾病谨慎使用。
⑸ 曾报道出血事件。只有已知出血风险患者期望获益胜过潜在风险时使用FEV。
⑹ 曾报道胃肠道穿孔。最近腹部手术治疗患者谨慎使用OFEV。发生胃肠道穿孔患者终止OFEV。只有有已知胃肠道穿孔风险如期望获益胜过潜在风险才使用OFEV。
不良反应
最常见不良反应(≥5%)是：腹泻，恶心，腹痛，呕吐，肝酶升高，食欲减退，头痛，体重减轻，和高血压。
药物相互作用
P-gp和CYP3A4抑制剂共同给药可能增加nintedanib暴露。密切监视患者对OFEV耐受性。
特殊人群中使用
⑴ 哺乳母亲：终止哺乳或终止药物，考虑药物对母亲重要性。
⑵ 肝受损：对有轻度肝受损患者监视不良反应和需要时考虑调整剂量或终止OFEV。有中度或严重肝受损患者中不建议使用OFEV。
⑶ 肾受损：未曾在有严重肾受损和肾病终末期患者研究OFEV的安全性和疗效。
⑷ 吸烟者：曾注意到吸烟者减低暴露可能改变OFEV疗效图形。

附：在日本上市的原处方资料：http://bij-kusuri.jp/medicine_data/ofe_cap/650168_39990A7M1026_1_02_content.htm
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上市国家：日本
原产地英文商品名:
Ofev Capsules（オフェブカプセル）100mg/capsules 28capsules/box
原产地英文药品名:
Nintedanib Ethanesulfonate
中文参考商品译名:
Ofev（オフェブカプセル）100毫克/胶囊 28胶囊/盒
中文参考药品译名:
尼达尼布
生产厂家中文参考译名:
勃林格殷格翰
生产厂家英文名:
Boehringer Ingelheim

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上市国家：日本
原产地英文商品名:
Ofev Capsules（オフェブカプセル）150mg/capsules 28capsules/box
原产地英文药品名:
Nintedanib Ethanesulfonate
中文参考商品译名:
Ofev（オフェブカプセル）150毫克/胶囊 28胶囊/盒
中文参考药品译名:
尼达尼布
生产厂家中文参考译名:
勃林格殷格翰
生产厂家英文名:
Boehringer Ingelheim

About OFEV(nintedanib) capsules
Indication and Usage
OFEV is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Elevated Liver Enzymes
The safety and efficacy of OFEV has not been studied in patients with moderate (Child Pugh B) or severe(Child Pugh C) hepatic impairment. Treatment with OFEV is not recommended in patients with moderate or severe hepatic impairment.
In clinical trials, administration of OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, GGT) and bilirubin. Liver enzyme increases were reversible with dose modification or interruption and not associated with clinical signs or symptoms of liver injury.
Conduct liver function tests (ALT, AST, and bilirubin) prior to treatment with OFEV, monthly for 3 months, and every 3 months thereafter, and as clinically indicated. Dosage modifications, interruption, or discontinuation may be necessary for liver enzyme elevations.
Gastrointestinal Disorders
Diarrhea
Diarrhea was the most frequent gastrointestinal event reported in 62% versus 18% of patients treated with OFEV and placebo, respectively. In most patients, the event was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhea led to permanent dose reduction in 11% of patients treated with OFEV compared to 0 placebo-treated patients. Diarrhea led to discontinuation of OFEV in 5% of the patients compared to <1% of placebo-treated patients.
Dosage modifications or treatment interruptions may be necessary in patients with adverse reactions of diarrhea. Treat diarrhea at first signs with adequate hydration and antidiarrheal medication (e.g., loperamide), and consider treatment interruption if diarrhea continues. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe diarrhea persists despite symptomatic treatment, discontinue treatment with OFEV.
Nausea and Vomiting
Nausea was reported in 24% versus 7% and vomiting was reported in 12% versus 3% of patients treated with OFEV and placebo, respectively. In most patients, these events were of mild to moderate intensity. Nausea led to discontinuation of OFEV in 2% of patients. Vomiting led to discontinuation of OFEV in 1% of the patients.
For nausea or vomiting that persists despite appropriate supportive care including anti-emetic therapy, dose reduction or treatment interruption may be required. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe nausea or vomiting does not resolve, discontinue treatment with OFEV.
Embryofetal Toxicity
OFEV is Pregnancy category D. It can cause fetal harm when administered to a pregnant woman. If OFEV is used during pregnancy, or if the patient becomes pregnant while taking OFEV, the patient should be advised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with OFEV and to use adequate contraception during treatment and at least 3 months after the last dose of OFEV.
Arterial Thromboembolic Events
Arterial thromboembolic events have been reported in patients taking OFEV. In clinical trials, arterial thromboembolic events were reported in 2.5% of patients treated with OFEV and 0.8% of placebo-treated patients. Myocardial infarction was the most common adverse reaction under arterial thromboembolic events, occurring in 1.5% of OFEV-treated patients compared to 0.4% of placebo-treated patients. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.
Risk of Bleeding
Based on the mechanism of action (VEGFR inhibition), OFEV may increase the risk of bleeding. In clinical trials, bleeding events were reported in 10% of patients treated with OFEV and in 7% of patients treated with placebo. Use OFEV in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.
Gastrointestinal Perforation
Based on the mechanism of action, OFEV may increase the risk of gastrointestinal perforation. In clinical trials, gastrointestinal perforation was reported in 0.3% of patients treated with OFEV, compared to 0 cases in the placebo-treated patients. Use caution when treating patients who have had recent abdominal surgery. Discontinue therapy with OFEV in patients who develop gastrointestinal perforation. Only use OFEV in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk.
ADVERSE REACTIONS
■Adverse reactions reported in ≥5% of patients treated with OFEV and more commonly than in patients treated with placebo included diarrhea (62% vs. 18%), nausea (24% vs.7%), abdominal pain (15% vs 6%), liver enzyme elevation (14% vs 3%), vomiting (12% vs 3%), decreased appetite (11% vs 5%), weight decreased (10% vs 3%), headache (8% vs 5%), and hypertension (5% vs 4%).
■The most frequent serious adverse reactions reported in patients treated with OFEV, more than placebo, were bronchitis (1.2% vs. 0.8%) and myocardial infarction (1.5% vs. 0.4%). The most common adverse events leading to death in patients treated with OFEV, more than placebo, were pneumonia (0.7% vs. 0.6%), lung neoplasm malignant (0.3% vs. 0%), and myocardial infarction (0.3% vs. 0.2%). In the predefined category of major adverse cardiovascular events (MACE) including MI, fatal events were reported in 0.6% of OFEV-treated patients and 1.8% of placebo-treated patients.
DRUG INTERACTIONS
P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers
Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of potent P-gp and CYP3A4 inhibitors (e.g., erythromycin) with OFEV may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of OFEV. Management of adverse reactions may require interruption, dose reduction, or discontinuation of therapy with OFEV. Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. Concomitant use of P-gp and CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) with OFEV should be avoided as these drugs may decrease exposure to nintedanib.
Anticoagulants
Nintedanib is a VEGFR inhibitor, and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.
USE IN SPECIFIC POPULATIONS
Nursing Mothers
■Excretion of nintedanib and/or its metabolites into human milk is probable. Because of the potential for serious adverse reactions in nursing infants from OFEV, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Hepatic Impairment
■Monitor for adverse reactions and consider dose modification or discontinuation of OFEV as needed for patients with mild hepatic impairment (Child Pugh A). Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with OFEV is not recommended.
Smokers
■Smoking was associated with decreased exposure to OFEV, which may alter the efficacy profile of OFEV. Encourage patients to stop smoking prior to treatment with OFEV and to avoid smoking when using OFEV.
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Through research, treatments and patient-centric support services, the Boehringer Ingelheim (BI) lung health portfolio is designed to help address the challenges people living with a lung disease face every day. Leveraging the company's cutting edge science and leadership in chronic obstructive pulmonary disease (COPD), BI is researching new treatment approaches where needs persist. It is the company's goal to make a difference in the lives of patients with COPD, asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory diseases.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
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In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.
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OFEV（尼达尼布）被纳入特发性肺纤维化国际治疗新指南
-新指南建议使用OFEV（尼达尼布）治疗特发性肺纤维化
-这项建议高度评价了OFEV®治疗患者的重要结果的潜在获益，包括根据用力肺活量（FVC）下降速率评估的疾病进展及死亡率
德国殷格翰2015年7月22日，特发性肺纤维化诊治国际循证指南（更新2011年指南）的发布，新指南建议临床医生使用OFEV®（尼达尼布）治疗特发性肺纤维化患者。
2015 ATS/ERS/JRS/ALAT特发性肺纤维化诊治国际循证指南（更新2011年指南）的发布，新指南建议临床医生使用OFEV ®（尼达尼布）治疗特发性肺纤维化患者。
委员会高度评价了OFEV®治疗患者的重要结果的潜在获益，包括根据用力肺活量（FVC）下降速率评估的疾病进展和死亡率。建议综合考虑预期治疗费用及潜在的重要不良反应。但是建议指出，OFEV®不会增加严重不良事件，很少患者因不良反应而中止使用研究药物。
英国伦敦皇家布朗普顿医院（Royal Brompton Hospital）呼吸内科顾问医生Dr Toby Maher评论说：“这些指南很重要，为医生改善这种破坏性极大的疾病，特发性肺纤维化的诊治提供了宝贵推荐意见。此外，这些新指南还明确强调了OFEV®治疗特发性肺纤维化的作用。”
勃林格殷格翰首席医学官Dr Christopher Corsico评论说：“国际指南纳入OFEV®治疗特发性肺纤维化是改善患者治疗的一次重要进步。直到最近，才有建议提出，有获批治疗可供选择。OFEV®使用方便，每日2次就可延缓范围广泛的多种特发性肺纤维化患者的疾病进展，减少肺功能年下降率50%。”
委员会分析了自2011年官方指南发布后收集的证据，并据此更新了治疗建议。 OFEV® 已开展两项重复性Ⅲ期试验（INPULSIS®-1和INPULSIS®-2），共有24个国家的1000多位患者参加研究，另外还进行过一项包括432位患者的II期试验（TOMORROW）。
指南联合委员会由国际领头呼吸学会的组织代表组成，包括美国胸科学会（American Thoracic Society，ATS）、欧洲呼吸学会（European Respiratory Society，ERS）、日本呼吸学会（Japanese Respiratory Society，JRS）和拉丁美洲胸科学会 (American Thoracic Association，ALAT）。
OFEV®的临床数据
INPULSIS®临床试验显示，OFEV®可持续稳定降低FVC年下降率，肺功能年下降率降低50%。 OFEV®是唯一能够显著降低裁定的特发性肺纤维化急性加重≠风险的治疗方案，急性加重风险下降68%。特发性肺纤维化急性加重的发病率与死亡率高，也是导致特发性肺纤维化患者住院和死亡的主要原因。
两项INPULSIS®试验最常见的不良事件均是轻度或中度胃肠道功能紊乱，通常可治，很少导致中止治疗。
关于特发性肺纤维化
特发性肺纤维化是一种致命性肺疾病，确诊后中位生存期为2-3年，可导致肺瘢痕进展、肺功能持续不可逆恶化和呼吸困难。特发性肺纤维化全球发病率达14-43/10万人，通常累及50岁以上人群。
这项条件性建议表示鼓励临床医生与患者讨论后再决定优选哪个治疗方案。