美国FDA批准(tbo-filgrastim)注射剂对严重中性粒细胞减少在某些癌症患者治疗
批准日期： 2012年8月29日；公司：Sicor Biotech
2012年8月29日美国食品药品监督管理局(FDA)批准Sicor Biotech公司的tbo-filgrastim减少有些患者接受癌症化疗经受严重中性粒细胞减少，与感染斗争的白细胞被称为嗜中性粒细胞减低的时间。
Tbo-filgrastim是意向为成年有癌症，除血液或骨髓癌症(非骨髓恶性病)和正在使用化疗药物引起骨髓中嗜中性粒细胞生成实质上减低。这种嗜中性减低可导致感染和发热(发热性中性粒细胞减少)。
Tbo-filgrastim刺激骨髓生成嗜中性粒细胞。在化疗治疗开始后24小时注射。
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：“支持性医疗产品，例如tbo-filgrastim，减低或允许从癌症治疗副作用更迅速回复”。
在一项348例成年晚期乳癌患者接受抗癌药物阿霉素和多西他奇治疗临床研究中评价Tbo-filgrastim。患者被随机赋予接受tbo-filgrastim，一种安慰剂，或非美国批准的非格司亭[filgrastim]产品，一种药物也刺激骨髓生成嗜中性粒细胞。The effectiveness of tbo-filgrastim的有效性是根据研究结果确定证明接受 tbo-filgrastim患者从严重中性粒细胞减少恢复比接受安慰剂3.8天减少1.1天。
在三项临床研究包括680例乳癌，肺癌，或非何杰金氏淋巴瘤成年接受高剂量化疗减低骨髓细胞(清骨髓化疗)中评价Tbo-filgrastim的安全性。接受tbo-filgrastim患者最常观察到副作用是骨痛。

tbo-filgrastim注射剂为皮下使用治疗：伴化疗中性粒细胞减少

美国初次批准：2012
 
一般描述
Tbo-filgrastim是一种无糖基化重组甲硫氨酰人粒细胞集落刺激生长因子(r-metHuG-CSF)通过重组DNA技术用细菌株大肠杆菌E coli K802制造。其分子量约18.8 kDa和由175个氨基酸组成。内源性人G-CSF是被糖基化和在其NH2末端没有附加的甲硫氨酸残基。
产品是一种无菌，澄明，无色，无防腐剂溶液含tbo-filgrastim，冰醋酸，山梨醇，聚山梨酯80，氢氧化钠，和注射用水。可得到产品在单次使用预装注射器含或300 μg或480 μg 的tbo-filgrastim分别为装填体积0.5 mL或0.8 mL。各种单次使用预装注射器见下表产品组成。

作用机制
Tbo-filgrastim是一种通过重组DNA技术生产的人粒细胞集落刺激因子(G-CSF)。Tbo-filgrastim与G-CSF受体结合和刺激嗜中性粒细胞增殖。已知G-CSF刺激定向粒细胞分化和有些终端细胞功能激活，增加嗜中性粒细胞计数和活性。

适应证和用途
Tbo-filgrastim是一种白细胞生长因子适用于在非-骨髓恶性病患者接受骨髓抑制抗癌药伴有临床意义发热性中性粒细胞减少的发生率，减少严重中性粒细胞减少时间。(1)

剂量和给药方法
（1）推荐剂量：5 μg/kg每天作为皮下注射给药。
（2）首次给药不早于骨髓抑制化疗后24小时。不要在化疗前24小时内给药。 (2.1)

剂型和规格
（1）300 μg/0.5 mL在单次使用预装注射器
（2）480 μg/0.8 mL在单次使用预装注射器(3)

禁忌证
无。

警告和注意事项
（1）脾破裂：如怀疑终止tbo-filgrastim (5.1)
（2）急性呼吸窘迫综合征(ARDS)监视和立即处理。如怀疑终止tbo-filgrastim (5.2) •
（3）过敏反应(血管神经性水肿，过敏性皮炎，药物超敏性，超敏性，皮疹，瘙痒皮疹和荨麻疹) (5. 3) •
（4）镰状细胞危象：可能发生严重和有时致命性危象。如怀疑终止tbo-filgrastim。(5.4)

不良反应
（1）对tbo-filgrastim最常见不良反应是骨痛。(6)
为报告怀疑不良反应，连续TEVA电话1-866-832-8537或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.

特殊人群中使用
（1） 在妊娠期间只有如果潜在获益升高对胎儿潜在风险，才应使用Tbo-filgrastim (8.1) •
（2）不知道tbo-filgrastim是否排泄在人乳汁中。(8.3) •
（3）尚未在18岁以下患者中确定tbo-filgrastim 的安全性和有效性。(8.4)

Tbo-filgrastim for Severe Neutropenia in Non-Myeloid Cancer Patients Approved

The FDA approved tbo-filgrastim to reduce the time of severe neutropenia experienced by certain patients receiving cancer chemotherapy. Neutropenia is a decrease in infection-fighting white blood cells called neutrophils.
Tbo-filgrastim is intended for use in adults who have cancers other than that of blood or bone marrow (non-myeloid malginancies) and are taking chemotherapy drugs that cause a substantial decrease in the production of neutrophils in the bone marrow. This reduction in neutrophils may lead to infection and fever (febrile neutropenia).
Tbo-filgrastim stimulates the bone marrow to increase the production of neutrophils. It is administered as an injection beginning 24 hours after chemotherapy treatment.
Tbo-filgrastim was evaluated in a clinical study of 348 adult patients with advanced breast cancer receiving treatment with the anti-cancer drugs doxorubicin and docetaxel. Patients were randomly assigned to receive tbo-filgrastim, a placebo, or a non-U.S.-approved filgrastim product, a drug that also stimulates neutrophil production by the bone marrow. The effectiveness of tbo-filgrastim was determined based on study results that showed that patients receiving tbo-filgrastim recovered from severe neutropenia in 1.1 days compared with 3.8 days in those receiving the placebo.
Tbo-filgrastim’s safety was evaluated in three clinical studies composed of 680 adults with breast cancer, lung cancer, or non-Hodgkin’s lymphoma who received high-dose chemotherapy that reduces bone marrow cells (myeloablative chemotherapy). The most common side effect observed in those receiving tbo-filgrastim was bone pain.
Tbo-filgrastim was approved in an original biologics license application (BLA). FDA has not approved tbo-filgrastim as a biosimilar to Neupogen (filgrastim), which is a previously licensed biological product that contains a related drug substance.
Tbo-filgrastim is manufactured by Sicor Biotech UAB, a member of Teva Corporation.

Tbo-filgrastim Side Effects
Serious Tbo-filgrastim side effects, including:
•Spleen rupture, which can cause death. Call your doctor right away if you have pain in your left upper stomach area or left shoulder area while taking tbo-filgrastim. This pain could mean your spleen is enlarged or ruptured.
•A serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Get medical help right away if you have any of these symptoms of Acute Respiratory Distress Syndrome (ARDS):
•fever
•shortness of breath
•trouble breathing
•Serious Allergic Reactions. If you have a serious allergic reaction during a tbo-filgrastim injection, your doctor will treat your allergic reaction and stop giving you the injections. Tell your doctor right away if you have any of these symptoms during or after your injection:
•a rash over the whole body
•shortness of breath
•trouble breathing (wheezing)
•dizziness
•swelling around the mouth or eyes
•fast heart rate
•sweating
•Severe Sickle Cell Crisis in people with a sickle cell disease. If you have sickle cell disease, talk to your doctor about the risks of taking tbo-filgrastim.
Tbo-filgrastim Directions:
Tbo-filgrastim is a prescription medicine:
•used in people with certain types of cancer (non-myeloid malignancies), who are receiving chemotherapy that affects the bone marrow
•given to help decrease the length of time that the number of certain white blood cells (neutrophils) are very low (severe neutropenia). Neutrophils are white blood cells that are important in fighting bacterial infections
It is not known if tbo-filgrastim is safe and effective in children under 18 years of age.