Synribo(omacetaxine mepesuccinate)
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免费版 |
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5.22 Kb |
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| 软件语言： |
简体中文 |
更新时间： |
2013-04-13 |
| 版本号： |
1.0 |
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Win2000/WinXP/Win2003 |
| 软件类别： |
国产软件 |
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★★★★★ |
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SYNRIBO
Pharmacological Class:
Protein synthesis inhibitor.
Active Ingredient(s):
Omacetaxine mepesuccinate 3.5mg/vial; lyophilized powder for SC injection after reconstitution; contains mannitol; preservative-free.
Company
Teva Pharmaceuticals
Indication(s):
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).
Pharmacology:
The mechanism of action of omacetaxine mepesuccinate has not been fully elucidated but includes inhibition of protein synthesis and is independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaebacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr-Abl oncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member.
Clinical Trials:
The efficacy of omacetaxine mepesuccinate was evaluated using a combined cohort of adult patients with CML from two trials. The combined cohort consisted of patients who had received 2 or more approved TKIs and had, at a minimum, documented evidence of resistance or intolerance to dasatinib and/or nilotinib. Patients were treated with omacetaxine mepesuccinate at a dose of 1.25mg/m2 administered subcutaneously twice daily for 14 consecutive days every 28 days (induction cycle). Responding patients were then treated with the same dose and twice daily schedule for 7 consecutive days every 28 days (maintenance cycle). Patients were allowed to continue to receive maintenance treatment for up to 24 months.
In the first trial, a total of 76 patients with chronic phase CML were included in the efficacy analysis. Thirty-six (47%) patients had failed treatment with imatinib, dasatinib, and nilotinib. Most patients had also received prior non-TKI treatments, most commonly hydroxyurea (54%), interferon (30%), and/or cytarabine (29%). At efficacy endpoint, 18% (14/76) achieved a major cytogenetic response (MCyR) with a mean time to MCyR onset of 3.5 months. The median duration of MCyR for these patients was 12.5 months (Kaplan-Meier estimate).
In the second trial, a total of 35 patients with accelerated phase CML were included in the efficacy analysis. Twenty-two (63%) of 35 patients with accelerated phase had failed treatment with imatinib, dasatinib, and nilotinib. Most patients had also received prior non-TKI treatments, most commonly hydroxyurea (43%), interferon (31%), and/or cytarabine (29%). At efficacy endpoint, 14% (5/35) achieved a major hematologic response (MaHR) with a mean time to response onset of 2.3 months. The median duration of MaHR for these patients was 4.7 months (Kaplan-Meier estimate).
Legal Classification:
Rx
Adults:
Induction: 1.25mg/m2 by SC injection twice daily for 14 consecutive days every 28 days, over a 28-day cycle. Repeat cycles every 28 days until hematologic response achieved. Maintenance: 1.25mg/m2 by SC injection twice daily for 7 consecutive days every 28 days, over a 28-day cycle. Dose adjustments and modifications: see full labeling.
Children:
Not established.
Warnings/Precautions:
Risk of myelosuppression (thrombocytopenia, neutropenia, anemia), hemorrhage. Monitor CBCs with platelets weekly during induction, initial maintenance cycles, and every 2 weeks during later cycles. Monitor glucose levels (esp. in diabetics). Avoid in poorly controlled diabetes until glycemic control is established. Elderly. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant anticoagulants, aspirin, NSAIDs if platelets <50,000/microliters; may increase risk of bleeding.
Adverse Reaction(s)
Thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, lymphopenia; bleeding, hyperglycemia.
How Supplied:
Single-use vial—1
LAST UPDATED:
3/4/2013
抗白血病新药Synribo获FDA批准
FDA于10月26日批准梯瓦新药synribo，用于治疗慢性粒细胞白血病（CML）。患者在接受至少两种酪氨酸激酶抑制剂后病情仍继续发展时，可使用synribo治疗。
Synribo主要通过阻断癌细胞发展过程中的特定蛋白起作用，注射方式为皮下，起初每天两次注射，连续注射14天，28天为一周期，直到白细胞计数正常。接着每天注射两次，连续注射7天，28天为一周期，直到患者仍能从中获益。
“一些患者抵抗或无法耐受其他FDA批准的药物治疗，但是synribo为他们提供了新的选择”，理查德帕兹德（ Richard Pazdur），FDA血液学和肿瘤学产品办公室主管说到，“synribo是近两月来批准的的第二种用于治疗CML药物”。在2012年9月4日，FDA批准bosulif用于治疗无法耐受其他疗法的急慢性费城染色体阳性的CML患者。
synribo的获批得益于FDA的加速审批程序。该程序有帮助于治疗严重疾病，FDA可根据药物在替代终点能否患者有益而批准药物。在公司做了证实药物临床受益和安全性的临床试验之后，该程序为病人更早地提供了使用新药的途径。
梯瓦公司的临床试验在一群经过至少两种酪氨酸激酶抑制剂治疗后仍持续进展的患者中进行，所有患者使用synribo治疗。在CML慢性期，synribo治疗后表达费城染色体基因突变的细胞比例降低。76例中有14例患者（18.4%）的比例减少持续3.5个月，中位数为12.5个月。在急性期，通过测定白细胞计数正常或没有白血病证据的患者人数来证实synribo的疗效。结果显示35例中有5例患者（14.3%）在平均维持2.3个月出现重大血液学反应，中位数是4.7个月。
在临床试验中，synribo主要副作用是血液血小板、红细胞、中性粒细胞及淋巴细胞数目减少，可能导致感染、发烧、腹泻、恶心、虚弱、疲劳、注射部位反应等不良反应。
完整说明
http://synribo.com/pdf/synribo_pi.pdf
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