SYNRIBO(omacetaxine mepesuccinate) injection, powder, lyophilized, for solution
[Cephalon, Inc.]
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SYNRIBO safely and effectively. See full prescribing information for SYNRIBO.
Initial U.S. Approval: 2012
INDICATIONS AND USAGE
SYNRIBO for Injection is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI). This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with SYNRIBO.
昨日宣布，FDA已批准Synribo注射液（omacetaxine mepesuccinate）用于对2种及以上酪氨酸激酶抑制剂（TKIs）有抗性或不耐受的慢性期（CP）或加速期（AP）慢性髓性白血病（CML）成人患者的治疗。该药是首个用于CML治疗的蛋白质合成抑制剂。
不过，目前还没有试验确证Synribo能够改善疾病相关症状或增加患者的生存，该药的获批是基于响应率数据。临床数据显示，该药物对替代终点（surrogate endpoint）有作用，FDA根据合理的推测认为该药能够为患者带来临床益处。Synribo的加速获批，目的是使CML患者能够更早地接受这种有前途的新药治疗。
梯瓦称，Synribo的获批是基于2项II期开放标签、多中心研究数据的汇总分析。汇总分析涉及已接受2种及以上已获批的TKIs且存在证据至少对达沙替尼和/或尼洛替尼有抗性或不耐受的患者。47%的CP患者及63%的AP患者经伊马替尼、达沙替尼、尼洛替尼治疗失败。大多数患者还接受了其他治疗药物，如羟基脲、干扰素、阿糖胞苷。
在治疗诱导期，每天注射2次Synribo，连续注射14天，28天为一周期；一旦取得治疗相应后，在维持治疗期，每天注射2次，连续注射7天，28天为一周期。
Synribo的作用机制尚未完全阐明，但包括抑制蛋白质合成。在体外实验中，Synribo直接独立地与Bcr-AbI结合，能够降低Bcr-AbI癌蛋白和McI-1的蛋白水平。此外，Synribo在野生型及T315I突变的Bcr-AbI CML小鼠模型中也有作用。
与Synribo相关的严重不良反应包括骨髓移植、出血、高血糖，其中骨髓移植及脑出血是致命性的。此外，女性患者在接受Synribo时，应避免妊娠
DOSAGE AND ADMINISTRATION
•Induction Dose: 1.25 mg/m2 administered by subcutaneous injection twice daily for 14 consecutive days of a 28-day cycle. (2.1)
•Maintenance Dose: 1.25 mg/m2 administered by subcutaneous injection twice daily for 7 consecutive days of a 28-day cycle. (2.2)
•Dose modifications are needed for toxicity. (2.3)
DOSAGE FORMS AND STRENGTHS
Single-use vial containing 3.5 mg of omacetaxine mepesuccinate as a lyophilized powder.
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
•Myelosuppression: severe and fatal thrombocytopenia, neutropenia and anemia. Monitor hematologic parameters frequently. (5.1)
•Bleeding: severe thrombocytopenia and increased risk of hemorrhage. Fatal cerebral hemorrhage and severe, non-fatal gastrointestinal hemorrhage. (5.1, 5.2).
•Hyperglycemia: glucose intolerance and hyperglycemia including hyperosmolar non-ketotic hyperglycemia. (5.3)
•Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential to avoid pregnancy. (5.4, 8.1)
ADVERSE REACTIONS
CML-Chronic Phase and Accelerated Phase: Most common adverse reactions (frequency ≥ 20%): thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-800-896-5855 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
See 17 for PATIENT COUNSELING INFORMATION
Revised: 10/2012
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FULL PRESCRIBING INFORMATION: CONTENTS*
* Sections or subsections omitted from the full prescribing
