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ZALTRAP(ziv-aflibercept)Injection for Intravenous Infusion
2012年8月3日美国食品药品监督管理局(FDA)批准Zaltrap(ziv-aflibercept)为与一种FOLFIRI (叶酸[folinic acid]，氟尿嘧啶[fluorouracil]和伊立替康[irinotecan])化疗方案联用治疗结肠直肠癌成年。
Zaltrap是一种血管生成抑制剂抑制对肿瘤的血管供应。意向为患者癌症已播散至机体其他部分(转移)和其肿瘤是对一种含奥沙利铂[Oxaliplatin]-化疗方案耐药或进展后的患者。
在美国结肠直肠癌是第四位最常被诊断癌症和第四领先癌症死亡原因。按美国国家卫生研究院估计2012年143,460美国人将被诊断结肠直肠癌和51,690例将死于此病。
FDA的药物评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“这个批准证实添加一种生物药物，Zaltrap，至一个常用化疗药物方案，FOLFIRI的的获益，”“注意到添加Zaltrap至FOLFIRI中位活存时间改善，伴反应率和延迟进展和生长改善。”
在一项随机临床研究1,226例转移结肠癌患者其癌症生长当接受基于奥沙利铂联合化疗，或其癌症被手术切除但在术后接受基于奥沙利铂联合化疗(辅助)治疗后6个月内恢复。参加者接受治疗直至其癌症进展或副作用变成不可接受的患者中评价Zaltrap的安全性和有效性。
研究被设计成测量总活存，或患者活存的时间长度。患者被赋予接受Zaltrap加FOLFIRI联用平均活存13.5个月，与之比较接受FOLFIRI加安慰剂患者平均12个月。患者接受Zaltrap加FOLFIRI联用肿瘤大小减小发生20%相比接受FOLFIRI加安慰剂为11%。
此外，临床试验证实无进展活存，或患者活存无癌症进展时间改善。对接受Zaltrap加FOLFIRI联用患者无进展活存为 6.9个月相比较接受 FOLFIRI加安慰剂患者为4.7个月。
正在批准的Zaltrap有一个黑框警告警惕患者和卫生保健专业人员药物可致严重和有时致命性出血，包括 胃肠道出血，和发生胃肠道道穿孔。Zaltrap还可能使伤口更难愈合。
接受 Zaltrap加FOLFIRI患者中观察到最常见副作用是减低白细胞计数，腹泻，口溃疡，疲乏，高血压，尿蛋白量增加，体重减轻，食欲减退，腹痛，和头痛。
Zaltrap由Bridgewater，N.J.-based sanofi-aventis公司制造。
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ZALTRAP® |
Prescribing Information |
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(ziv-aflibercept) Injection for Intravenous Infusion |
Rx only |
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use ZALTRAP safely and effectively. See full prescribing information for ZALTRAP.
ZALTRAP® (ziv-aflibercept)
Injection for Intravenous Infusion
Initial U.S. Approval: 2012
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WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING
See full prescribing information for complete boxed warning.
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Hemorrhage: Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in patients who have received ZALTRAP. Do not administer ZALTRAP to patients with severe hemorrhage. (5.1)
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Gastrointestinal Perforation: Discontinue ZALTRAP therapy in patients who experience GI perforation. (5.2)
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Compromised Wound Healing: Discontinue ZALTRAP in patients with compromised wound healing. Suspend ZALTRAP for at least 4 weeks prior to elective surgery, and do not resume for at least 4 weeks following major surgery and until the surgical wound is fully healed. (5.3)
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RECENT MAJOR CHANGES
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Dosage and Administration (2.3) |
09/2014 |
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Warnings and Precautions (5.7) |
10/2013 |
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INDICATIONS AND USAGE
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ZALTRAP, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. (1)
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DOSAGE AND ADMINISTRATION
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4 mg/kg as an intravenous infusion over 1 hour every 2 weeks. (2.1, 2.4)
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Do not administer as an intravenous (IV) push or bolus. (2.4)
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DOSAGE FORMS AND STRENGTHS
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Single-use vials: 100 mg/4 mL (25 mg/mL), 200 mg/8 mL (25 mg/mL) (3)
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CONTRAINDICATIONS
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None (4)
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WARNINGS AND PRECAUTIONS
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Adverse reactions, sometimes severe and life-threatening or fatal, have been seen in clinical trials with ZALTRAP, including:
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Fistula Formation: Discontinue ZALTRAP if fistula occurs. (2.2, 5.4)
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Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend ZALTRAP if hypertension is not controlled. Discontinue ZALTRAP if hypertensive crisis develops. (2.2, 5.5)
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Arterial Thromboembolic Events (ATE) (e.g., transient ischemic attacks, cerebrovascular accident, angina pectoris): Discontinue ZALTRAP if ATE develops. (5.6)
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Proteinuria: Monitor urine protein. Suspend ZALTRAP when proteinuria ≥ 2 grams per 24 hours. Discontinue ZALTRAP if nephrotic syndrome or thrombotic microangiopathy (TMA) develops. (2.2, 5.7)
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Neutropenia and Neutropenic Complications: Delay administration of ZALTRAP/FOLFIRI until neutrophil count is ≥ 1.5 × 109/L. (5.8)
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Diarrhea and Dehydration: Incidence of severe diarrhea and dehydration is increased. Monitor elderly patients more closely. (5.9, 8.5)
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Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue ZALTRAP. (5.10)
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ADVERSE REACTIONS
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Most common adverse reactions (all grades, ≥20% incidence and at least 2% greater incidence for the ZALTRAP/FOLFIRI regimen) were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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USE IN SPECIFIC POPULATIONS
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Pregnancy: Based on animal data, ZALTRAP may cause fetal harm. (8.1)
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Nursing Mothers: Discontinue drug or nursing taking into account the importance of the drug to the mother. (8.3)
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Females and Males of Reproductive Potential: Use highly effective contraception during and up to a minimum of 3 months after the last dose (8.8)
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See 17 for PATIENT COUNSELING INFORMATION |
Revised: 09/2014 |
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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| 以下是“全球医药”详细资料 |
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