【药品名称】诺其 NovoSeven

【通 用 名】注射用重组人凝血因子VIIa

【适 应 症】用于下列患者群体的出血发作及预防; 在外科手术过程中或有创操作中的出血。 
·凝血因子Ⅷ或Ⅸ的抑制物〉5BU的先天性血友病患者； 　
·预计对注射凝血因子Ⅷ或凝血因子 Ⅸ,具有高记忆应答的先天性血友病患者；
·获得性血友病患者； 
·先天性FVII缺乏症患者； 
·具有GP II b-IIIa和/或HLA抗体和既往或现在对血小板输注无效或不佳的血小板无力症患者。

【用法用量】诺其?治疗推荐的标准剂量为90～120mcg/kg，初始时每间隔2小时予此剂量输注，然后逐渐延长给药间隔。临床研究证实，存在有抑制物的患者，无论是存在有同种异体抗体的血友病A和血友病B患者，还是存在有自身抗体的获得性血友病患者，诺其?90 mcg/kg的剂量均可有效（有效率80～90％）并且安全地确保止血。

【不良反应】
罕见严重的不良反应，但有异常情况时，请与医生联系。极少的情况下可能会出现出血、皮疹和发烧。产品上市后发生过的严重不良反应有：
1、动脉血栓事件：如心肌梗塞或缺血，脑血管疾患和肠梗塞。所有这些患者均由于年龄、动脉硬化病史或现患有“特殊警告及特殊注意事项”中所列疾病而具有血栓性疾病倾向。
2、静脉血栓事件：如肺栓塞及血栓静脉炎。所有这些患者均由于年龄、手术后卧床或中心静脉导管而具有栓塞性疾病倾向。患者因年龄、既往栓塞史（动脉硬化病史、手术后卧床或中心静脉导管史）而具有栓塞性疾病倾向，用药时应密切监察。
3、出血：严格按照“用量”项下所推荐的剂量注射者无一例引起出血的报告。
在临床试验中有凝血异常如血小板计数降低，纤维蛋白原减少和出现D-二聚体的报告。除一例病例外，没有出现与凝血异常相关的临床症状。这一特殊的病例由于肌坏死，具有弥散性血管内凝血倾向。具有弥散性血管内凝血倾向的患者，用药时应密切监察。
上市至今，有一例没有临床症状的凝血异常病例报告。
在包含血小板减少症患者的临床试验中，有一例过敏反应报告。这名患者对其它几种药品有过敏反应史，在接受重组人凝血因子Ⅶa治疗后发生了过敏反应。上市至今，没有过敏反应的报告。具有过敏反应史的患者，用药时应密切监察。

【药物相互作用】使用本品前，应咨询医生有关同时使用其它药品的问题。

【注意事项】
使用本品前，如有下列情况，请告知医生：
1、刚做过外科手术；
2、患有挤压性损伤；
3、患有血栓形成性疾病或进行性动脉粥样硬化性疾病；
4、患有败血症。
重度出血者须到医院注射本药。
轻度或中度出血者可在家里注射重组人凝血因子VIIa（NovoSeven），应立即向医生或医院汇报重组人凝血因子Ⅶa的使用剂量和效果（如：电话联系）。必要时与血液科专家保持密切联系。
如果用药24小时后，出血未得到控制，则不能再继续在家治疗，应到医院就诊。
将本品置于远离儿童的地方。

【禁 忌】
对本品中含有的活性成份，赋形剂，或小鼠、仓鼠或牛蛋白过敏者禁用。

【孕妇及哺乳期妇女用药】妊娠妇女应在有明确需要时才使用本品。若正在哺乳,应停止哺乳或停止用药。

【贮 藏】
本品应存放于2oC-8oC（冰箱中）；在-包装盒内避光保存；请勿冰冻以免损坏溶剂瓶；最好配制后立即使用；请勿将配制好的重组人凝血因子VIIa(NovoSeven）持续储存在注射器中。

【原产地英文商品名】NOVOSEVEN RT 2000mcg/vial
【原产地英文药品名】FACTOR VIIA,RECOMB(BHK CELLS)
【中文参考商品译名】
注：以下产品不同规格和不同价格，购买时请以电话咨询为准！

·诺其 RT 2000微克/瓶

·诺其 RT 1000微克/瓶

·诺其 RT 5000微克/瓶

·诺其 RT 8000微克/瓶

·诺其 1.2毫克冻干粉(60KIU,60000IU)/瓶
【中文参考药品译名】重组人凝血因子VIIA,RECOMB(BHK细胞)
【生产厂家中文参考译名】诺和诺德
【生产厂家英文名】Novo Nordisk

 Brand Names: NovoSeven, NovoSeven RT

Generic Name: coagulation factor VIIa (injection) (Pronunciation: koe AG yoo LAY shun FAK tor )

What is coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Coagulation factor VIIa is a man-made protein that is similar to a natural protein in the body that helps the blood to clot.

Coagulation factor VIIa is used to treat or prevent bleeding in people with hemophilia A or hemophilia B, or factor VII deficiency.

Coagulation factor VIIa may also be used for other purposes not listed in this medication guide.

What are the possible side effects of coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:
fever;
any bleeding that will not stop;
feeling like you might pass out;
urinating less than usual or not at all;
sudden numbness or weakness, especially on one side of the body;
sudden headache, confusion, problems with vision, speech, or balance; or
pain or swelling in one or both legs.

Less serious side effects may include:
headache;
joint pain;
nausea, vomiting;
swelling;
mild itching or rash; or
pain, redness, swelling, or irritation where the medicine was injected.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Before using this medication, tell your doctor if you are allergic to any drugs, or if you have coronary artery disease (hardening of the arteries), a history of stroke or heart attack, a severe injury or infection, or if you are allergic to mouse, hamster, or pork proteins.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Carry an ID card or wear a medical alert bracelet stating that you have a bleeding disorder in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know about your condition.

What should I discuss with my healthcare provider before using coagulation factor VIIa (NovoSeven, NovoSeven RT)?
If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before using coagulation factor VIIa, tell your doctor if you have:
coronary artery disease (hardening of the arteries);
a history of stroke or heart attack;
a severe injury or infection; or
if you are allergic to mouse, hamster, or pork proteins.

FDA pregnancy category C. Coagulation factor VIIa may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether coagulation factor VIIa passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Coagulation factor VIIa is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to use your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of needles, IV tubing, and other items used in giving the medicine.

You may need to mix coagulation factor VIIa with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication. Do not use the medication if it has changed colors or has any particles in it. Call your doctor for a new prescription.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Carry an ID card or wear a medical alert bracelet stating that you have a bleeding disorder in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know about your condition.

NovoSeven should be stored in the refrigerator. Do not freeze. Avoid exposing the medication to sunlight.

NovoSeven RT may be stored at cool room temperature away from moisture, heat, and light.

After mixing NovoSeven RT with a diluent, you may keep it at room temperature or in the refrigerator and use it within 3 hours. Do not freeze or store the mixture in a syringe.

What happens if I miss a dose (NovoSeven, NovoSeven RT)?
Contact your doctor if you miss a dose of this medication.

What happens if I overdose (NovoSeven, NovoSeven RT)?
Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of coagulation factor VIIa is not expected to produce life-threatening symptoms.

What should I avoid while using coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using this medication.

What other drugs will affect coagulation factor VIIa (NovoSeven, NovoSeven RT)?
Tell your doctor about all other medications you use, especially medications used to treat severe bleeding episodes, such as:
aminocaproic acid (Amicar); or
tranexamic acid (Cyklokapron).

This list is not complete and there may be other drugs that can interact with coagulation factor VIIa. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?
Your pharmacist can provide more information about coagulation factor VIIa.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

诺其 Novoseven

什么是重组活化凝血因子Ⅶ？

诺其（Novoseven®），重组活化人凝血因子VII，由诺和诺德公司研制生产，用于治疗存在有因子VIII（FVIII）和因子IX（FIX）抗体（抑制物）的先天性血友病和继发性血友病患者的自发性或手术性出血。这种重组蛋白是从新生仓鼠肾细胞克隆的人因子Ⅶ基因中表达出来的，生产的整个过程或最终产品都没有用到任何人源性的材料。

分子结构图 （略）

药理剂量的诺其能够在‘活化’血小板表面将FⅩ转化为FⅩa。经过一系列复杂的步骤，FⅩa在损伤部位形成血凝块。非常重要的一点是：正常情况下，血小板只在损伤局部活化——因此能够防止在不需要形成血栓的部位形成血栓。这种独特的作用机制可以解释为什么诺其在没有因子Ⅷ和Ⅸ的情况下也能够安全有效地止血。

诺其产品图（略）

目前，诺其已在全世界范围内被批准用于存在有抑制物的先天性血友病的治疗；在欧洲，诺其亦被批准用于获得性血友病的治疗。

以往对于存在有抑制物的患者，可行的治疗方案不多，而且这些治疗方法在安全性和有效性方面均存在有局限。如何治疗这些患者发生的威胁生命和肢体功能的严重出血，仍然是一个巨大的挑战。许多患者死于无法控制的出血；因出血而导致的重度关节损害的问题仍然十分严重；对有抑制物的患者进行手术时如何止血，尤其是一个特殊的难题。在过去，由于没有有效的药物可以保证手术安全地进行，大部分存在有抑制物的血友病患者均无法进行择期的手术治疗。

因为可避免人类病毒的污染，基因工程制备的重组因子浓缩剂的问世，使血友病患者治疗的安全性得到了明显的提高。然而，由于许多存在有抑制物的血友病患者还在接受着血浆和血液制品的治疗，发生感染性和非感染性并发症的危险性仍然存在，其中一些甚至是致命的（如全身性感染和急性肺损伤）。有些血浆衍生凝血因子浓缩剂可引起血栓症.

诺其治疗推荐的标准剂量为90～120mcg/kg，初始时每间隔2小时予此剂量快速输注，然后减少给药间隔。临床研究证实，存在有抑制物的患者，无论是存在有同种异体抗体的血友病A和血友病B患者，还是存在有自身抗体的获得性血友病患者，诺其90 mcg/kg的剂量均可有效（有效率80～90％）并且安全地确保止血。

存在有抑制物的血友病患者，早期开始治疗，例如将诺其作为一线药物，疗效最佳。

因子VII缺乏的患者曾被予以诺其20～30mcg/kg治疗。对这一患者群治疗的经验正在迅速地积累(17,18)。给予诺其治疗后，存在有抑制物的血友病患者或因子VII缺乏的患者均可以进行手术治疗，而其发生严重的出血或合并症的危险性很低(2,4,18)。诺其在治疗先天性和获得性血友病领域取得的成功，使其相关研究已扩展到血友病以外的其它出血性疾患的治疗上。
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- Recombinant Factor VIIa

NovoSeven® (recombinant activated clotting factor VII ~ rFVIIa) has been developed by Novo Nordisk A/S for the treatment of spontaneous and surgical bleedings in haemophilia A and B patients with antibodies (inhibitors) against factors VIII (FVIII) and IX (FIX), respectively.1,6,10-14

Before NovoSeven® was launched, there were few therapeutic alternatives for inhibitor patients, and those that did exist had limited safety and efficacy.15

• Effective treatment of life and limb-threatening bleeds is still a challenge, particularly for inhibitor patients, and many die from uncontrollable bleeds. These patients also continue to develop severe joint damage. Furthermore, surgery in patients with inhibitors presents a particular challenge to haemostasis management and, in the past, inhibitor patients have often been denied elective surgical procedures.
• Treatment safety has been improved for haemophilia patients by the development of new genetically engineered recombinant factor concentrates, which are free of human virus. However, as many inhibitor patients still receive plasma-based products, the risk of viral transmission and thrombosis still exists.16,17

Clinical trials have clearly demonstrated that administration of NovoSeven® in doses of 90 µg/kg effectively (80-90%) and safely ensures haemostasis in inhibitor patients of all types, regardless of whether they have allo-antibodies, as in haemophilia A and B1,6,10-14or auto-antibodies as in acquired haemophilia.11Inhibitor patients treated with NovoSeven® can undergo major surgery with a very small risk of uncontrolled haemorrhage and complications.6,11,19

NovoSeven® is now indicated to stop bleeding in just one single 270ug/kg dose*. This is in addition to the existing dosing guideline; 90 µg/kg, repeated as necessary every 2–3 hours.

This new dosing guideline can reduce multiple intravenous infusions thereby helping to preserve the status of the vein. Now patients with haemophilia and inhibitors and their carers can experience less interruption to their daily lives.

* Single Dose NovoSeven® 270µg/kg approved in EU. Pending approval in other countries. Ref: NovoSeven® Prescribing Information, 2007.

NovoSeven® is a registered trademark of Novo Nordisk Health Care AG.