注射用Kyprolis（carfilzomib）已获美国FDA及欧洲批准上市对多发性骨髓瘤患者新治疗 FDA的药物评价和研究中心血液学和肿瘤室主任Richard Pazdur，M.D 说：“Kyprolis的批准对尽管使用可得到的治疗其疾病已进展的多发性骨髓瘤患者提供治疗选择，”“在过去十年通过为多发性骨髓瘤药物不断的进展，提供这种疾病改善治疗。我们受到鼓舞。” 批准日期：2012年7月20日  公司： Onyx Pharmaceuticals，Inc/Amgen KYPROLIS™ (卡非佐米 carfilzomib)注射用，为静脉使用 美国初次批准：2012 作用机制 Carfilzomib是一种四肽基环氧骨架蛋白酶体抑制剂不可逆地结合至20S蛋白酶体含苏氨酸N-端活性部位，26S蛋白酶体内蛋白水解核心颗粒。Carfilzomib有抗增殖和凋亡活性在体外在实体和血液学中粒细胞。在动物中，carfilzomib抑制 蛋白酶体活性在血液和组织和在多发性骨髓瘤，血液学，和实体瘤模型中延迟肿瘤生长。 适应症和用途 Kyprolis是一种蛋白酶体抑制剂适用为治疗多发性骨髓瘤患者，患者曾接收至少两种既往治疗包括硼替佐米和一种免疫调节药和曾证实疾病进展或末次治疗完成的60天内。批准是根据反应率。尚未证明临床获益，例如活存或症状改善。 剂量和给药方法 （1）每周连续2天历时2至10分钟静脉给药共三周（第1，2，8，9，15，和16天），接着12-天休息期（第17至28天）。 （2）推荐疗程1剂量是20mg/m2/day和如果耐受增加第2疗程剂量和随后疗程剂量至27mg/m2/day。 （3）给药前和后水化患者。 （4）在所有第1疗程剂量前用地塞米松预先给药。在第一疗程剂量递增期，和如果发生或再次出现输注反应症状时。 （5）根据毒性修改给药。 剂型和规格 单次使用小瓶：60mg无菌冻干粉。 禁忌证 无 警告和注意事项 （1）心脏不良反应包括心衰和缺血：监视心脏并发症。及时治疗和中止Kyprolis。 （2）肺动脉高压：如果怀疑中止给药。 （3）肺部并发症：监视和立即处理呼吸困难，中断Kyprolis直至症状已解决或恢复至基线。 （4）输注反应：用地塞米松预先给药预防。 （5）忠告患者如果发生症状立即寻医学注意。 （6）血小板减少：监视血小板计数；当临床上指示减低或中断给药。 （8）胚胎胎儿毒性：Kyprolis可致胎儿危害。有生育能力女性当正在治疗时应避免成为妊娠。 不良反应 最常报道的不良反应（发生率 ≥ 30%）是疲乏，贫血，恶心，血小板减少，呼吸困难，腹泻，和发热。 特殊人群中使用 正在透析患者：透析操作后给予Kyprolis。 贮存和处置 未开封小瓶应准存在冰箱（2°C至8°C; 36°F至46°F）。保留在原包装避光保护。 KYPROLIS(carfilzomib)for Injection Important Safety Information Cardiac Toxicities •New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration. •Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment. •While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure. •Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up. Acute Renal Failure •Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate. Tumor Lysis Syndrome •Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved. Pulmonary Toxicity •Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug‐induced pulmonary toxicity, discontinue KYPROLIS. Pulmonary Hypertension •Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment. Dyspnea •Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit/risk assessment. Hypertension •Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with KYPROLIS. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment. Venous Thrombosis •Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks. •Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus dexamethasone. Infusion Reactions •Infusion reactions, including life‐ hreatening reactions, have occurred in patients receiving KYPROLIS. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur. Hemorrhage •Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate. Thrombocytopenia •KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate. Hepatic Toxicity and Hepatic Failure •Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate. Thrombotic Microangiopathy •Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known. Posterior Reversible Encephalopathy Syndrome (PRES) •Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro‐ adiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known. Embryo-fetal Toxicity •KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. •Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions •The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia. •The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral. Please see full Prescribing Information. Indications •KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. •KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. --------------------------------------------------- 产地国家: 美国 原产地英文商品名: Kyprolis Powder 30mg Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 30毫克/瓶 中文参考药品译名: 卡非佐米 生产厂家英文名: Onyx Pharmaceuticals --------------------------------------------------- 产地国家: 美国 原产地英文商品名: Kyprolis Powder 60mg/Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 60毫克/瓶 中文参考药品译名: 卡非佐米 生产厂家英文名: Onyx Pharmaceuticals --------------------------------------------------- 产地国家: 瑞士 原产地英文商品名: Kyprolis Powder 60mg/Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 60毫克/支 中文参考药品译名: 卡非佐米 生产厂家英文名: Amgen Switzerland AG --------------------------------------------------- 产地国家: 荷兰 原产地英文商品名: Kyprolis Powder 10mg/Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 10毫克/支 中文参考药品译名: 卡非佐米 生产厂家英文名: Amgen Ltd --------------------------------------------------- 产地国家: 荷兰 原产地英文商品名: Kyprolis Powder 30mg/Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 30毫克/支 中文参考药品译名: 卡非佐米 生产厂家英文名: Amgen Ltd --------------------------------------------------- 产地国家: 荷兰 原产地英文商品名: Kyprolis Powder 60mg/Vial 原产地英文药品名: Carfilzomib 中文参考商品译名: Kyprolis 粉剂 60毫克/支 中文参考药品译名: 卡非佐米 生产厂家英文名: Amgen Ltd 荷兰处方资料附件：https://www.medicines.org.uk/emc/medicine/31222