FDA批准惠氏Xyntha用于治疗A型血友病

2月21日，美国FDA批准了一种治疗A型血友病的新药—Xyntha，该药由美国费城的惠氏制药公司生产。A型血友病是一种罕见的遗传性凝血功能障碍疾病，在美国大约有15000名患者，并且这些患者几乎全是男性，新疗法的批准对这些患者而言无疑有深远的影响。
这项新疗法被称为Xyntha 抗血友病因子（重组）血浆/白蛋白疗法，这种药物是基因工程改良版的凝血因子VIII，其本质就是凝血过程中所必需的一种蛋白质。如大家所知，凝血因子VIII被称为抗血友病因子，而A型血友病患者正是缺少或缺失该因子。
Xyntha已被批准用于控制和预防A型血友病患者的出血，包括自发性的出血以及意外事故或者损伤所致的出血。除此之外，Xyntha还可以用于预防这类患者的手术出血。
Xyntha的生产采用的是DNA重组技术，该技术使得科学家们能够合成出特定性状的DNA双链，例如能够产生特定的蛋白质。
Xyntha是修改了中国仓鼠卵巢细胞（CHO）基因所生产出的凝血因子VIII。这些CHO细胞都不会接触任何感染因素，并且Xyntha的生产过程中还有一个专门的病毒灭活步骤。同时，这些细胞不会和任何来源于人或动物的物质接触，因此更大程度的减少了任何感染传染病的危险，该产品给广大A型血友病患者提供了一个新选择。
在临床试验中，Xyntha被证明可以有效地预防或控制A型血友病患者的出血，其中还包括预防手术中的出血。一般来说，最常见的不良反应是头痛。至于接受Xyntha治疗以防止外科手术出血的患者，最常见的不良反应则是发烧。无论哪一个研究报道的多数不良反应都被认为只是轻度或中度。
此外，在89位接受Xyntha治疗50天的患者中，有2位患者表现出对凝血因子VIII抑制，这是因为他们的体内产生了抗体对抗了凝血因子VIII。

XYNTHA

Indication(s):

In hemophilia A: to control bleeding episodes, and for surgical prophylaxis.

Pharmacology:

Hemophilia A is a disease in which the patient is deficient in the coagulation factor VIII, a pivotal protein in the clotting cascade.The administration of Xyntha to patients with hemophilia A can temporarily correct the coagulation defect by increasing plasma factor VIII activity.

Clinical Trials:

The efficacy of this product was evaluated in a study in which patients received Xyntha on a prophylaxis treatment regimen with on-demand treatment given as clinically indicated. This study enrolled 94 patients with baseline factor VIII activity ≤2%. They all received Xyntha in the open-label period, and 53 were given Xyntha for treatment of 187 bleeding episodes. Most of the bleeding episodes resolved with 1 or 2 infusions. In an ongoing, open-label study of Xyntha in surgical prophylaxis, an interim analysis showed that for 21 surgical patients, the investigators’ ratings of efficacy at the end of surgery and at the end of the initial post-op period were excellent or good for all assessments.

Legal Classification:

Rx

Adults:

Individualize and titrate.Give by IV infusion over several minutes.One IU of factor VIII per kg raises the plasma factor VIII activity by about 2 IU/dL.To determine dose:Required units = body wt (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).Minor bleeds: factor VIII level required is 20–40 IU/dL or % of normal, repeat infusion every 12–24 hours as needed for at least 1 day, until resolution.Moderate bleeds: 30–60 IU/dL or % of normal; repeat infusion every 12–24 hours for 3–4 days or until hemostasis.Major bleeds: 60–100 IU/dL or % of normal, repeat infusion every 8–24 hours until resolution.Minor surgical procedures:30–60 IU/dL or % of normal, repeat infusion every 12–24 hours for 3–4 days or until hemostasis.Major surgery: 60–100 IU/dL or % of normal; repeat infusion every 8–24 hours until hemostasis and wound healing occurs.

Children:

Consult manufacturer (limited pharmacokinetic data available; studies are ongoing).

Warnings/Precautions:

Use only under the supervision of a properly trained physician.Monitor for development of neutralizing antibodies (“inhibitors”); may need dose adjustment.Pregnancy (Cat.C).Labor & delivery.Nursing mothers.

Adverse Reaction(s):

Hypersensitivity reactions/anaphylaxis, pyrexia, headache, GI upset, asthenia.

How Supplied:

Kit—1 (w. diluent, supplies)

Last Updated:

1/16/2009

Xyntha(抗血友病因子(重组),无血浆/白蛋白)部份处方说明

批准日期：2008年2月21日；公司：Wyeth Pharmaceuticals Inc.。

一般描述：

抗血友病因子(重组)，无血浆/白蛋白，XYNTHA中的活性成分。是一种用重组DNA技术生产的重组第VIII凝血因子，为第VIII凝血因子缺乏症治疗中使用。XYNTHA中的抗血友病因子(重组)，无血浆/白蛋白是已知纯化的糖蛋白，分子质量接近170 kDa，由1438个氨基酸组成，不含B-结构区。XYNTHA抗血友病因子(重组)无血浆/白蛋白的氨基酸序列与人第VIII凝血因子的型式有可比性，分子质量90 80 kDa。XYNTHA中抗血友病因子(重组)无血浆/白蛋白，被遗传工程中国仓鼠卵巢血浆(CHO)细胞株分泌。细胞株 is grown in a 化学上确定含重组胰岛素细胞培养介质中生长，但不含任何从人或动物来源任何材料。用一种工艺纯化XYNTHA中抗血友病因子(重组)无血浆/白蛋白， 其中包括一系列层析步骤，其中一步用基于专利合成多肽亲和配基的亲和层析。工艺还包括溶剂-去垢剂病毒灭活步骤和保留病毒毫微米过滤步骤。

适应证和用途：

XYNTHA是一种抗血友病因子适用于：
1.  在血友病A患者中控制和预防出血发作。
2.  在血友病A患者中手术预防。

剂量和给药方法：

用下列公式确定需要的剂量：

需要的单位 = 体重(kg) × 需要第VIII凝血因子升高(IU/dL或正常的%) × 0.5 (IU/kg / IU/dL)
静脉注射配制产品的频数决定于出血发作的类型和推荐的治疗医生。

剂型和规格：

可得到的XYNTHA粉为在单次使用小瓶中250、500、1000、或2000 IU。

禁忌证：

无

警告和注意事项：
1.  可能有过敏反应和严重超过敏反应。这类反应发生时，应中断治疗和应给予适当治疗。
2.    接受含第VIII凝血因子产品患者中曾检测到发生活性-中和抗体。如未达到期望的血浆第VIII凝血因子活性水平，或如用适当剂量出血未被控制，应进行用一种测定第VIII凝血因子抑制剂浓度的分析。
3. 患者可能发生对产品中存在含量的仓鼠蛋白超敏。

不良反应

最常见不良反应在研究1中(24%受试者)是头痛和在研究2是发热 (41%受试者)。
研究过程期间2/89例受试者(完成50天暴露)发生抑制剂。89例受试者完成50天暴露观察到2例抑制剂与用XYNTHA抑制剂形成率的概率95%一致，低于用贝叶斯分析4.17%。
药物相互作用：
无
在特殊人群中的使用：
儿童受试者中用XYNTHA得到的药代动力学资料有限(N=7)。

Xyntha
Generic Name: antihemophilic factor (recombinant) (ant ee hee moe FIL ik FAK tor (ree KOM bin ant))
Brand Names: Advate rAHF-PFM, Helixate FS, Kogenate FS, Kogenate FS with Bioset, Recombinate, Refacto, Xyntha

What is Xyntha?
Xyntha contains antihemophilic factor, a naturally occurring protein in the blood that helps blood to clot. A lack of antihemophilic factor VIII is the cause of hemophilia A.

Xyntha works by temporarily raising levels of factor VIII in the blood to aid in clotting. It is used to treat or prevent bleeding episodes in adults and children with hemophilia A. Xyntha is also used to control bleeding related to surgery or dentistry in a person with hemophilia.

Xyntha may also be used for other purposes not listed here.

Important information about Xyntha
Do not use Xyntha if you have ever had a severe allergic reaction to antihemophilic factor in the past, or if you are allergic to mouse or beef proteins.
Before using Xyntha, your specific blood clotting disorder must be diagnosed as factor VIII deficiency. Recombinant antihemophilic factor will not treat von Willebrand disease.

Your body may develop antibodies to Xyntha, making it less effective. Call your doctor if Xyntha seems to be less effective in controlling your bleeding.

To be sure Xyntha is helping your condition and is not causing harmful effects, your blood may 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 hemophilia in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you have a bleeding or blood-clotting disorder.

Before using Xyntha
Do not use Xyntha if you have ever had a severe allergic reaction to antihemophilic factor in the past, or if you are allergic to mouse or beef proteins.
Before using Xyntha, your specific blood clotting disorder must be diagnosed as factor VIII deficiency. Recombinant antihemophilic factor will not treat von Willebrand disease.

FDA pregnancy category C. This medication 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 recombinant antihemophilic factor passes into breast milk or if it could harm a nursing baby. Do not use Xyntha without telling your doctor if you are breast-feeding a baby.

How should I use Xyntha?
Use Xyntha exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label. Always check the strength of the medicine on the label to be sure you are using the correct potency.

Xyntha 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 Xyntha 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.

Xyntha comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Always wash your hands before preparing and giving your injection.
Xyntha must be mixed with a liquid (diluent) before injecting it. If you store your medicine in the refrigerator, take a medicine and diluent vial out of the refrigerator and allow each to reach room temperature before mixing them.

Gently swirl the medicine and diluent to mix them and allow the medicine to completely dissolve.

After mixing the medicine and diluent, the mixture should be kept at room temperature and must be used within 3 hours. Do not put mixed medicine into the refrigerator.
Draw your dose into a syringe only when you are ready to give yourself an injection. Each vial is for one use only. After measuring your dose, throw the vial away, even if there is medicine left in it.

Do not use Xyntha if it has changed colors or has any particles in it. Call your doctor for a new prescription.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Xyntha is usually given every 8 to 24 hours for 1 to 4 days, depending on the reason you are using the medication.

To be sure Xyntha is helping your condition and is not causing harmful effects, your blood may need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Your body may develop antibodies to Xyntha, making it less effective. Call your doctor if Xyntha seems to be less effective in controlling your bleeding.

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

Xyntha should be stored under refrigeration at a temperature of 2? to 8?C (36?to 46?F). Xyntha may also be stored at room temperature not to exceed 25?C (77?F) for up to 3 months, until the expiration date. You should write in the space provided on the outer carton, the date the product was placed at room temperature. At the end of the 3-month period, the product should not be put back into the refrigerator, but should be used immediately or discarded. The diluent syringe may be stored at 2? to 25?C (36? to 77?F). Freezing should be avoided to prevent damage to the pre-filled diluent syringe. During storage, avoid prolonged exposure of Xyntha vial to light. Do not use Xyntha after the expiration date on the label. Follow the storage directions on the medicine label.

Throw away any leftover medicine and diluent if the expiration date has passed.

What happens if I miss a dose?
Xyntha is sometimes used only as needed, so you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

What happens if I overdose?
Call your doctor if you think you have used too much of this medicine. An overdose of Xyntha is not expected to produce life-threatening symptoms.

What should I avoid while using Xyntha?
Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using Xyntha.

Xyntha side effects
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; feeling light-headed, fainting; swelling of your face, lips, tongue, or throat. Stop using Xyntha and call your doctor at once if you have any of these serious side effects:
chest pain;
easy bruising, increased bleeding episodes; or
bleeding from a wound or where the medicine was injected.

Less serious side effects may include:
sore throat, cough, runny nose;
fever or chills;
mild nausea, vomiting;
unusual or unpleasant taste in your mouth;
skin itching or rash;
warmth, redness, itching, or tingling under your skin;
joint pain or swelling;
dizziness;
headache; or
swelling, stinging, or irritation where the injection was given.

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 other drugs will affect Xyntha?
There may be other drugs that can affect Xyntha. 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.

More Xyntha resources
Xyntha Side Effects (in More Detail)
Xyntha Use in Pregnancy & Breastfeeding
Xyntha Support Group
0 Reviews for Xyntha - Add your own review/rating

Compare Xyntha with other medications
Hemophilia A

Where can I get more information?
Your pharmacist can provide more information about Xyntha.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Xyntha 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.

辉瑞公司用于A型血友病的预填充双室注射器获得美国FDA的行政批准--------一种用于血友病的革新性产品

辉瑞公司宣布用于A型血友病的预填充双室注射器---XYNTHA®（无添加血浆/白蛋白的抗血友病因子）获得美国FDA的行政批准。XYNTHA是凝血因子VIII产品，主要用于控制和预防A型血友病患者（先天VIII因子不足或典型血友病）偶发出血情形和外科预防的治疗，由于该产品不含血管假性血友病因子，因此不能用于治疗遗传性假血友病。

“预填充双室注射器不仅具有革新性而且使用便捷，省略了转换步骤，无疑此产品的批准对血友病患者来说具有里程碑的意义，” 作为辉瑞生物制品部的市场总裁Emil Andrusko谈到，“辉瑞一直致力于血友病研究领域，不仅有像这种便捷式的XYNTHA预填充双室注射器，同时也在进一步研究已通过临床试验的其他蛋白产品，如Xa因子、VIIa因子。