近日，由Genmab研发的抗癌药于2009年10月26日就在美国获得FDA批准，而在2010年4月19在欧盟获得上市批准，2013年3月25日在日本获得上市批准，商品名Arzerra®。Ofatumumab是一种以CD20为靶向的溶细胞单克隆抗体，其能结合表达于正常B淋巴细胞和B细胞慢性淋巴性白血病(CLL)表面的CD20分子，并通过抗体依赖的细胞毒作用(ADCC)和补体依赖的细胞毒作用(CDC)杀伤肿瘤B细胞。
ARZERRA(奥法木单抗[ofatumumab])注射液，用于静脉注射
初步批准日期:2009年
警告:乙型肝炎病毒再次激活
渐进多焦点的脑白质病，请参阅完整的处方信息的完整框警告。
•乙型肝炎病毒(HBV)重新激活，在某些情况下导致暴发肝炎、肝功能衰竭和死亡。
进展性多灶性白质脑病(PML)导致死亡。
最近的重大变化
适应症和用法,延长治疗在慢性淋巴细胞白血病:1/2016
适应症和用法，复发性CLL：8/2016，1/2016年1月推荐给药方案
剂量和管理,管理:8/2016
剂量和管理,Pre-medication: 1/2016
作用机制
Ofatumumab分别与CD20分子的大小细胞外环结合。cd20分子表达于正常B淋巴细胞(B-成熟前B淋巴细胞)和B细胞CLL。c20分子不会从细胞表面脱落，也不会在抗体结合后内化。ofatumumab的Fab结构域与CD20分子结合，Fc结构域介导免疫功能，导致体外b细胞裂解。数据表明，细胞裂解的可能机制包括细胞毒性和抗体依赖性细胞介导的细胞毒性。
适应症和用法
ARZERRA (ofatumumab)是一种cd20导向的细胞溶解单克隆抗体，用于慢性淋巴细胞白血病(CLL)的治疗:与氯丁苯磺酸联合使用，用于治疗以前未治疗的CLL患者，认为氟达拉滨类药物治疗不合适。
联合氟达拉滨和环磷酰胺治疗复发CLL患者。
对于完全或部分有反应的病人，在至少两行复发或进展性CLL治疗后进行延长治疗。
用于治疗CLL难治性氟达拉滨和阿仑单抗患者。
剂量和管理
稀释后作为静脉输液给药。不要皮下给药，也不要静脉给药或静脉给药。
CLL联合氯丁苯磺酸建议用量及时间表:
第1天服用300毫克，第8天服用1000毫克(第1周期)
在随后28天疗程的第一天服用1000毫克，最少3次疗程，直至最佳反应或最多12次疗程。
复发期CLL联合氟达拉滨、环磷酰胺推荐剂量及疗程为:
第1天服用300毫克，第8天服用1000毫克(第1周期)
在随后的28天周期的第1天服用1000毫克，最多6个周期。
CLL延长治疗推荐剂量和时间为:
第一天300毫克，然后
1周后第8天服用1000毫克，随后服用
7周后服用1000毫克，之后每8周服用一次，为期2年。
难治性CLL的推荐剂量和时间表为:
初始剂量300毫克，1周后7次，每周2000毫克，4周后4次，每4周2000毫克。
管理适当监控和处理注入反应的设施。
用对乙酰氨基酚、抗组胺和皮质类固醇进行预用药。
剂型和强度
100mg/5ml一次性小瓶静脉输液。
1000mg/50mL单瓶静脉输液。
禁忌症
没有。
警告和预防措施
输液反应:用皮质类固醇、对乙酰氨基酚、抗组胺药物进行预处理。在输液过程中监测患者。发生灌注中断反应。
肿瘤溶解综合征:对高危患者进行TLS预测;抗高尿酸和水合作用。
细胞减少症:出现中性粒细胞减少症、贫血和血小板减少症。晚期和长期的中性粒细胞减少症也可能发生。定期监测完整的血液计数。
不良反应
CLL:常见不良反应(10%)为输液反应和中性粒细胞减少。
复发性CLL:常见不良反应(>10%)为输液反应、中性粒细胞减少、白细胞减少、发热性中性粒细胞减少。
延长治疗慢性淋巴细胞白血病:常见的不良反应(≥10%)wereinfusion反应,嗜中性白血球减少症,上呼吸道感染。
难治性慢性淋巴细胞白血病:常见的不良反应(10%)嗜中性白血球减少症,肺炎、发热、咳嗽、腹泻、贫血、疲劳、呼吸困难、皮疹、恶心、支气管炎和上呼吸道感染。
若要报告可疑的不良反应，请联系NovartisPharmaceuticals Corporation(电话1-888-669-6682)或FDA(电话1-800-FDA-1088)或www.fda.gov/medwatch。
在特定人群中使用
妊娠:可能导致胎儿b细胞耗竭。
包装提供/存储和处理
ARZERRA(ofatumumab)是一种无菌、透明、乳白色、无色、无防腐剂的液体浓缩物(20mg/mL)，用于稀释和静脉注射。每瓶含有100毫克ofatumumabin 5毫升溶液或1000毫克ofatumumab 50毫升溶液。
ARZERRA如下:
ARZERRA 100MG SDV 3X5ML  OFATUMUMAB  NOVARTIS PHARM CORP  NDC：78066913
ARZERRA 1000MG SDV 50ML  OFATUMUMAB  NOVARTIS PHARM CORP  NDC：78069061
ARZERRA 20MG/ML 50ML SDV PF 1/EA  OFATUMUMAB  NOVARTIS PHARMACEUTICALS CORPO  NDC：00078-0690-61
ARZERRA 20MG/ML 5ML SDV PF 3/PAC  OFATUMUMAB  NOVARTIS PHARMACEUTICALS CORPO  NDC：00078-0669-13
商店ARZERRA冷藏28C(3646F)。不冻结。小瓶应避光。
完整说明书附件：
1）：https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/arzerra.pdf
2）https://www.patient.novartisoncology.com/?site=PATSUAAvuAA201710271&source=01025
ARZERRA(ofatumumab) Injection, for intravenous infusion
ARZERRA (ofatumumab) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. The effectiveness of ARZERRA is based on the demonstration of durable objective responses. No data demonstrate an improvement in disease-related symptoms or increased survival with ARZERRA.
Important Safety Information
Highlights of Warnings and Precautions
Infusion Reactions: Premedicate with an intravenous corticosteroid(as appropriate), an oral analgesic, and an oral or intravenous antihistamine. Monitor patients closely during infusions. Interrupt infusion if infusion reactions occur.
Cytopenias: Monitor blood counts at regular intervals for neutropenia and thrombocytopenia.
Progressive Multifocal Leukoencephalopathy (PML): Monitor neurologic function and discontinue ARZERRA if PML is suspected.
Hepatitis B Infection and Reactivation: Screen high-risk patients.
Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis.
Infusion Reactions
ARZERRA can cause serious infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema.
Infusion reactions occur more frequently with the first 2 infusions.
Premedicate with acetaminophen, an antihistamine, and a corticosteroid. Interrupt infusion for infusion reactions of any severity. Institute medical management for severe infusion reactions including angina, or other signs and symptoms of myocardial ischemia. In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5 patients developed Grade 3 bronchospasm during infusion. Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2,000 mg), and less frequently during subsequent
infusions.
Cytopenias
Prolonged (>1 week) severe neutropenia and thrombocytopenia can occur with ARZERRA. Monitor complete blood counts (CBC) and platelet counts at regular intervals during therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed >Grade 3 neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia >2 weeks in duration.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur with ARZERRA.
Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms.
Discontinue ARZERRA if PML is suspected and initiate eva luation for PML including consultation with a neurologist, brain MRI, and lumbar puncture.
Hepatitis B Infection and Reactivation
Fulminant and fatal hepatitis B virus (HBV) infection and reactivation can occur in patients following treatment with ARZERRA.
Screen patients at high risk of HBV infection before initiation of ARZERRA.
Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12 months following the last infusion of ARZERRA.
Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis, and institute appropriate treatment.
Insufficient data exist regarding the safety of administration of ARZERRA in patients with active hepatitis.
Intestinal Obstruction
Obstruction of the small intestine can occur in patients receiving ARZERRA. Perform a diagnostic eva luation if obstruction is
suspected.
Immunizations
The safety of immunization with live viral vaccines during or following administration of ARZERRA has not been studied.
Do not administer live viral vaccines to patients who have recently received ARZERRA. The ability to generate an immune response to any vaccine following administration of ARZERRA has not been studied.
Most Common Adverse Reactions
In the pivotal study (total population, n=154) the most common adverse reactions (>10%, all grades) were neutropenia, followed by pneumonia (23%), pyrexia (20%), cough (19%), diarrhea (18%), anemia (16%), fatigue (15%), dyspnea (14%), rash (14%), nausea (11%), bronchitis (11%), and upper respiratory tract infections (11%).
Most Common Serious Adverse Reactions
In the pivotal study (total population, n=154), where ARZERRA was administered at 2,000 mg beginning with the second dose for 11 doses, the most common serious adverse reactions were infections(including pneumonia and sepsis), neutropenia, and pyrexia.
A total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced >Grade 3 infections, of which 19 (12%) were fatal.
The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%. 
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附件:


2011122123255618.PDF   
2011122123255124.PDF