美国食品药品监督管理局(FDA)9月12日批准Aubagio(teriflunomide，特立氟胺)，每天1次的片剂治疗成人复发型多发性硬化症(MS)。 FDA的药物评价和研究中心神经学产品分部主任Russell Katz博士说：“在一项临床试验中，用Aubagio患者的复发率比服用安慰剂患者低约30%”。“多发性硬化症可损害运动，感觉，和思维，所以给患者多种治疗选择很重要。” MS 是一种中枢神经系统的慢性、炎性、自身免疫疾性病，疾病破坏脑与身体其他部位的练习。它是造成年轻患者神经疾病最常见的原因，女性发病是男性的至少两倍。对大多数MS患者来说，疾病早期有多次复发和缓解，随着时间的推移，缓解可能不完全，导致渐进性恶化。 在临床试验中患者经历的最常见副作用包括腹泻，肝功能试验异常，恶心和脱发。 药物包含一个黑框警告，警告处方者和患者注意肝脏问题的风险，包括死亡，以及出生缺陷的风险。患者开始服用Aubagio前和治疗期间，医生应定期对其进行肝功能检测。 黑框警告还提到，根据动物研究，药物可能会对胎儿造成危害。基于这个理由，Aubagio被标记为妊娠X类，即意味着育龄妇女在用药前妊娠检验需阴性，且治疗期间使用有效的避孕措施。 Aubagio由赛诺菲 (Sanofi)及其子公司健赞（GenzyME）制造。 批准日期：September 12，2012；公司：Sanofi AUBAGIO (teriflunomide)片为口服给药. 美国初次批准：2012 一般描述 AUBAGIO(teriflunomide)是一种口服从头嘧啶合成DHO-DH酶的抑制剂，有化学名(Z)-2-Cyano-3-hydroxy-but-2-enoic acid-(4-trifluoromethylphenyl)-amide。其分子量为270.21，和经验式为C12H9F3N2O2有以下化学结构： Teriflunomide是一种白色至几乎白色粉在丙酮中难溶，略溶于聚乙二醇和醇，极微溶于异丙醇和实际上几乎不溶于水。 Teriflunomide被制剂化为薄膜衣片为口服给药。AUBAGIO片含7 mg或14 mg的teriflunomide和以下无活性成分：一水乳糖，玉米淀粉，羟丙基纤维素，微晶纤维素，羟基乙酸淀粉钠，和硬脂酸镁。为14 mg片包膜是羟丙纤维素，二氧化钛，滑石粉，聚乙二醇和靛蓝胭脂红铝色淀。7 mg片包膜处理这些包括氧化铁黄。 作用机制 Teriflunomide，一种免疫调制药有抗炎性质，抑制双氢乳清酸酯脱氢酶一种涉及嘧啶的从头合成的线粒体酶。在多发性硬化症中teriflunomide发挥其治疗效应的确切机制不知道但可能涉及减少在CNS中激活的淋巴细胞数. 适应证和用途 AUBAGIO是一种嘧啶合成抑制剂适用于有多发性硬化症的复发型患者治疗。(1) 剂量和给药方法 7 mg或14 mg口服每天1次，有或无食物。(2) 剂型和规格 7 mg和14 mg薄膜衣片(3) 禁忌证 严重肝受损(4.1，5.1) 妊娠 (4.2，5.2，8.1) 当前来氟米特[leflunomide]治疗 (4.3) 警告和注意事项 （1）给予考来烯胺[cholestyramine]或活性碳共11天可能加速AUBAGIO的消除(5.3) （2）AUBAGIO可能减低WBC。开始AUBAGIO前应得到最近CBC。监测感染的体征和症状。考虑暂停用AUBAGIO治疗和严重感染的情况中使用加速消除方法步骤。有活动性感染患者中不要开始AUBAGIO(5.4) （3）周围神经病变：如患者发生症状与周围神经病变一致，评价患者和考虑终止AUBAGIO和使用加速消除方法步骤(5.5) （4）急性肾衰/高钾血症：在肾衰或高钾血症症状患者中监测肾功能和钾(5.6，5.7) （5）严重皮肤反应：停止AUBAGIO和使用加速消除方法步骤 (5.8) （6）血压：治疗开始时测量。治疗期间适当监测和处理 (5.9) 不良反应 最常见不良反应(10%和大于安慰剂2%)：ALT增加，脱发，腹泻，流感，恶心，和感觉异常。 (6) 报告怀疑不良反应，联系Genzyme Corporation电话1-800-745-4447或FDA电话1-800-FDA-1088或www.fda.gov/medwatch. 药物相互作用 被CYP2C8代谢药物：监测患者因teriflunomide可能增加其暴露 (7) Teriflunomide可能增加炔雌醇[ethinylestradiol]和左炔诺孕酮[levonorgestrel]的暴露。选择一种适当口服避孕药 (7) 被CYP1A2代谢药物：监测患者因teriflunomide可能减低其暴露 (7) 华法林[Warfarin]：监测INR因teriflunomide可能减低INR (7) 特殊人群中使用 在妊娠中禁忌；得到妊娠注册(4.2，8.1) 如何供应/贮存和处理 AUBAGIO可得到7 mg和14 mg片。 14 mg片是淡蓝色至粉蓝色，五角形薄膜衣片在一侧引诱剂量强度数14和另一侧刻有公司的标志. The 7 mg片 is 非常亮-蓝灰色至浅绿蓝色，六角形薄膜衣片，一侧印有有剂量强度“7”和另一侧刻有公司的标志。每片含7 mg teriflunomide. AUBAGIO 14 mg片被供应为： NDC 58468-0210-2 为28片纸盒含1纸袋包括 2个折叠泡卡，每泡卡14片 NDC 58468-0210-1 为5片纸盒有5片泡卡 AUBAGIO 7 mg片供应如下： NDC 58468-0211-1 为28片纸盒含1纸袋包括 2个折叠泡卡，每泡卡14片 NDC 58468-0211-2 为5片纸盒有一个5片泡卡。 贮存在68°F至77°F (20°C至25°C)外出时允许 59°F和86°F (15°C和30°C)间。 Aubagio Approved for Relapsing Multiple Sclerosis AUBAGIO (teriflunomide) 14mg tablets by Genzyme Genzyme announced that the FDA has approved Aubagio (teriflunomide tablets), a new once-daily, oral treatment indicated for patients with relapsing forms of multiple sclerosis (MS). Aubagio has shown significant efficacy in reducing relapses, slowing the progression of physical disability, and reducing the number of brain lesions as detected by MRI. The approval was based on efficacy data from the Phase 3 TEMSO (TEriflunomide Multiple Sclerosis Oral) trial evaluating more than 5,000 patients in 36 countries. Aubagio 14mg significantly reduced the annualized relapse rate (P=0.0005) and the time to disability progression (P=0.0279) at two years vs. placebo in patients with relapsing forms of MS.  Additionally, Aubagio 7mg significantly reduced the annualized relapse rate (P=0.0002) in the trial. Aubagio is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for Aubagio is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system. Aubagio will be supplied as 7mg and 14mg tablets. Genzyme expects to make Aubagio available on October 1st, 2012 Generic Name: teriflunomide Date of Approval: September 12, 2012 Company: Genzyme Corporation Treatment for: Multiple Sclerosis FDA Approves Aubagio The U.S. Food and Drug Administration (FDA) has approved Aubagio (teriflunomide) as a new once-daily, oral treatment indicated for patients with relapsing forms of multiple sclerosis (MS). Aubagio has shown significant efficacy across key measures of MS disease activity, including reducing relapses, slowing the progression of physical disability, and reducing the number of brain lesions as detected by MRI. Aubagio is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for Aubagio is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system (CNS). The Aubagio label includes a boxed warning citing the risk of hepatotoxicity and, teratogenicity (based on animal data). Aubagio Medication Guide Read this Medication Guide before you start using Aubagio and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about Aubagio? Aubagio may cause serious side effects, including: Liver problems: Aubagio may cause serious liver problems that may lead to death. Your risk of liver problems may be higher if you take other medicines that also affect your liver. Your doctor should do blood tests to check your liver: within 6 months before you start taking Aubagio once a month for 6 months after you start taking Aubagio Call your doctor right away if you have any of the following symptoms of liver problems: nausea vomiting stomach pain loss of appetite tiredness your skin or the whites of your eyes turn yellow dark urine Harm to your unborn baby: Aubagio may cause harm to your unborn baby. Do not take Aubagio if you are pregnant. Do not take Aubagio unless you are using effective birth control. If you are a female, you should have a pregnancy test before you start taking Aubagio. Use effective birth control during your treatment with Aubagio. After stopping Aubagio, continue using effective birth control until you have blood tests to make sure your blood levels of Aubagio are low enough. If you become pregnant while taking Aubagio or within 2 years after you stop taking it, tell your doctor right away. For men taking Aubagio: If your female partner plans to become pregnant, you should stop taking Aubagio and ask your doctor how to quickly lower the levels of Aubagio in your blood. If your female partner does not plan to become pregnant, you and your female partner should use effective birth control during your treatment with Aubagio. Aubagio remains in your blood after you stop taking it, so continue using effective birth control until Aubagio blood levels have been checked and they are low enough. Aubagio may stay in your blood for up to 2 years after you stop taking it. Your doctor can prescribe a medicine to help lower your blood levels of Aubagio more quickly. Talk to your doctor if you want more information about this. What is Aubagio? Aubagio is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS). Aubagio can decrease the number of MS flare-ups (relapses). Aubagio does not cure MS, but it can help slow down the physical problems that MS causes. It is not known if Aubagio is safe and effective in children. Who should not take Aubagio? Do not take Aubagio if you: have severe liver problems are pregnant or are of childbearing age and not using effective birth control take a medicine called leflunomide What are the ingredients in Aubagio? Active ingredient: teriflunomide Inactive ingredients: lactose monohydrate, corn starch, hydroxypropylcellulose, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, talc, polyethylene glycol and indigo carmine aluminum lake. Aubagio side effects Aubagio may cause serious side effects, including: See What is the most important information I should know about Aubagio? decreases in your white blood cell count. Your white blood cell counts should be checked before you start taking Aubagio. When you have a low white blood cell count you: may have more frequent infections. You should have a skin test for TB (Tuberculosis) before you start taking Aubagio. Tell your doctor if you have any of these symptoms of an infection: fever tiredness body aches chills nausea vomiting should not receive certain vaccinations during your treatment with Aubagio and for 6 months after your treatment with Aubagio ends. numbness or tingling in your hands or feet that is different from your MS symptoms. You have a greater chance of getting peripheral neuropathy if you: are over 60 years of age take certain medicines that affect your nervous systemhave diabetes Tell your doctor if you have numbness or tingling in your hands or feet that is different from your MS. kidney problems. Tell your doctor if you have pain in your side (flank pain). high potassium levels in your blood. Tell your doctor if you have nausea that does not go away or a racing heartbeat. serious skin problems. Tell your doctor if you have any skin problems such as redness and peeling. new or worsening breathing problems. Tell your doctor if you have shortness of breath or coughing with or without fever. high blood pressure. Your doctor should check your blood pressure before you start taking Aubagio and while you are taking Aubagio. The most common side effects of Aubagio include: increases in the results of blood tests to check your liverhair thinning or loss (alopecia) diarrhea flu nausea burning or prickling feeling in your skin (paraesthesia)