GAZYVA^TM(obinutuzumab), in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

Important Safety Information

 Boxed WARNINGS: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

• Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies, including GAZYVA. Screen all patients for HBV infection before treatment initiation. Monitor HBV positive patients during and after treatment with GAZYVA. Discontinue GAZYVA and concomitant medications in the event of HBV reactivation.
• Progressive Multifocal Leukoencephalopathy (PML) including fatal PML, can occur in patients receiving GAZYVA.

Additional Warnings and Precautions

• Infusion Reactions: GAZYVA can cause severe and life-threatening infusion reactions. For patients with Grade 4 infusion reactions, including but not limited to anaphylaxis, acute life-threatening respiratory symptoms, or other life-threatening infusion reaction, stop and permanently discontinue GAZYVA therapy. Premedicate patients with acetaminophen, antihistamine, and a glucocorticoid. Closely monitor patients during the entire infusion. Infusion reactions within 24 hours of receiving GAZYVA have occurred. For Grades 1, 2, or 3 infusion reactions, interrupt or discontinue infusion for reactions.
• Tumor Lysis Syndrome (TLS): TLS can occur within 12-24 hours after the first infusion. Patients with high tumor burden and/or high circulating lymphocyte count (>25 x 10⁹/L) are at greater risk for TLS and should receive appropriate tumor lysis prophylaxis with anti-hyperuricemics and hydration beginning 12-24 hours prior to the infusion of GAZYVA.
• Infections: Serious bacterial, fungal, and new or reactivated viral infections can occur during and following GAZYVA therapy. Do not administer GAZYVA to patients with an active infection.
• Neutropenia: Severe neutropenia can occur. Monitor patients with Grade 3 to 4 neutropenia frequently with regular laboratory tests until resolution. Neutropenia can also be of late onset and/or prolonged.
• Thrombocytopenia: Severe thrombocytopenia can occur. Monitor patients with Grade 3 or 4 thrombocytopenia for platelet counts and bleeding frequently until resolution. Management of hemorrhage may require blood product support.

Company:
Genentech, Inc.

Indications for GAZYVA:
Treatment of patients with previously untreated chronic lymphocytic leukemia (CLL), in combination with chlorambucil.

Adult Dose for GAZYVA:
Premedicate (eg, glucocorticoid, APAP, antihistamine) before each infusion. Give by IV infusion for 6 treatment cycles (28 days duration). Cycle 1: 100mg on Day 1 at 25mg/hr over 4 hours; 900mg on Day 2 at 50mg/hr, may increase at 50mg/hr every 30mins (max 400mg/hr); 1000mg on Days 8 and 15 at 100mg/hr, may increase by 100mg/hr increments every 30mins (max 400mg/hr); Cycles 2–6: 1000mg on Day 1 at 100mg/hr, may increase by 100mg/hr increments every 30mins (max 400mg/hr). Infusion rate and premedication adjustments: see full labeling.

Children's Dose for GAZYVA:
Not established.

Pharmacological Class:
Cytolytic monoclonal antibody (CD20-directed).

Warnings/Precautions:
Risk of hepatitis B virus (HBV) reactivation; immediately discontinue and any concomitant chemotherapy if occurs. Screen for HBV infection prior to initiation; if positive evidence, monitor and consider antiviral therapy. Discontinue treatment and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressives if PML develops. Monitor closely for infusion reactions; if Grade 4: discontinue permanently; if Grade 3: interrupt until resolved; if Grade 1 or 2: interrupt or reduce the infusion rate and manage symptoms. Preexisting cardiac or pulmonary conditions: monitor more frequently during and post-infusion period for severe reactions. Risk of TLS in high tumor burden and/or high circulating lymphocyte count (>25 x 109/L): prophylaxis with antihyperuricemics and hydration. Active infection: do not administer. Monitor for bleeding; obtain blood and platelet counts frequently. Risk of neutropenia; give antimicrobial prophylaxis. Pregnancy (Cat. C). Nursing mothers: not recommended.

Interactions:
Concomitant live viral vaccines: not recommended. Consider withholding antihypertensives for 12hrs prior to, during, and for 1hr after infusion until BP is stable.

Adverse Reactions:
Infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, musculoskeletal disorders.

How Supplied:
Single-use vial (40mL)—1
治疗慢性淋巴细胞白血病的药物Gazyva获得FDA批准
慢性淋巴细胞性白血病是一种血液及骨髓疾病，该疾病通常会缓慢恶化。根据美国国家癌症研究所预测，今年将有15680美国人被确诊患有这种疾病且4580人将会死于慢性淋巴细胞性白血病。
11月1日，美国食品药品管理局（FDA）批准Gazyva（Obinutuzumab）与苯丁酸氮芥联合用药共同治疗先前未经处理的慢性淋巴细胞性白血病（CLL）。
Gazyva是首款以突破性指定治疗药物获得FDA批准。该药物在获得支持市场批准的生物制品许可后由赞助商提议进入指定药物范围，很快获得FDA批准。 一般情况下，初步临床证据表明某药物可在病情严重或威胁到生存患者的治疗中能够提供实质性改善者，在赞助商提议下就可获得批准。
Gazyva是通过帮助免疫系统中的某些细胞来攻击肿瘤细胞发挥其作用。它将与苯丁酸氮芥联合用药治疗慢性淋巴细胞性白血病，在这之前使用其它一些药物用于该病治疗。
FDA也授予了Gazyva优先审评资格，因为这款药物的安全性和有效性被证实其对危重病症的治疗有可能会带来明显的改善。并且，由于这款药物也可用于治疗一种罕见疾病，从而获得FDA授予的孤儿药资格。
Gazyva获批用于治疗慢性淋巴细胞性白血病是基于一项由356名受试者参与的随机、非盲、多中心临床研究。在先前未经治疗的慢性淋巴细胞性白血病受试 者身上将Gazyva与苯丁酸氮芥合并用药与苯丁酸氮芥单独用药进行了研究对比。Gazyva与苯丁酸氮芥合并用药的受试者的疾病无进展生存期得到明显改 善，平均增加23个月；而单独苯丁酸氮芥用药受试者的疾病无进展生存期仅为11.1个月。
在Gazyva与苯丁酸氮芥合并用药受试者中所观察到的最常见副作用包括输注相关反应、抗感染的白细胞降低（中性粒细胞减少症）、血液中血小板水平降低（血小板减少症）、红细胞水平降低（贫血）、肌痛和骨痛（肌肉骨骼疼痛）和发烧（发热）。
Gazyva获批时带有一项框栏警告，提示这款药物与乙型肝炎病毒的再活化及一种罕见疾病有关，该罕见疾病能损伤大脑白质中包裹和保护神经的物质（进行性 多灶性白质脑病）。这些是与该类药物中其它单克隆抗体共有的已知风险，而罕见病例在Gazyva的其它临床试验受试者身上得到了证实。患者应该被告知这些 风险，并对患者乙型肝炎病毒及其再活化的风险进行评估。
Gazyva由位于加利福尼亚州南圣弗朗西斯科的Roche集团下属子公司Genetech上市销售。