美国FDA批准新生物制品Xeomin(incobotulinumtoxinA) 批准日期：2010年8月2日；公司：Merz Pharmaceuticals, LLC 注射用XEOMIN (incobotulinumtoxinA) for injection, 肌肉内注射用 最初美国批准： 2010年 一般描述 XEOMIN的活性组分是肉毒毒素类型A，由Hall strain肉毒梭状芽胞杆菌[Clostridium botulinum]血清型A株发酵生产.。从培养上清纯化肉毒毒素复合物和然后从蛋白分离活性组分(血凝素和非-血凝素)通过一些列步骤产生活性神经毒素有分子量150 kDa，无附属蛋白。XEOMIN是无菌，白色至淡白色冻干粉，在用0.9%注射液盐水，USP (无防腐剂)配制后意向肌肉内注射，一小瓶XEOMIN含50或100单位 的incobotulinumtoxinA，1 mg人白蛋白，和4.7 mg蔗糖。一个单位相当于小鼠中位致死剂量(LD50)当配制好产品在确定条件下腹膜内注射入小鼠。进行分析方法是对XEOMIN特异的，XEOMIN的生物学活性单位不能转换成任何用其他特异性分析评估的其它肉毒毒素的单位。 作用机制 XEOMIN通过抑制从周边胆碱能神经末梢释放乙酰胆碱，阻断在神经肌肉接头处胆碱能传递。这个抑制作用按照以下顺序：神经毒素结合至胆碱能神经末梢，神经毒素的内化进入神经末梢，分子的轻链部分转位入神经末梢的胞液，和SNAP25的酶裂解，对释放乙酰胆碱重要的突触前靶蛋白。通过形成新神经末梢重新建立脉冲传递。 适应证和用途 XEOMIN是一种乙酰胆碱释放抑制剂和神经肌肉阻断剂适用于治疗： 1）有颈部肌张力失常成年，以减低严重程度异常头位置和颈疼痛在肉毒毒素-未治过和既往治疗过患者两者(1.1). 2）眼睑痉挛既往用onabotulinumtoxinA(Botox?)治疗过的成年(1.2). 剂量和给药方法 XEOMIN制剂是意向为肌肉内注射。最佳剂量和在被治疗肌肉的注射部位数应对每个患者个体化并由医生决定。 颈部肌张力失常 (2.1) 1）每治疗期[session]推荐总剂量是120单位。较高剂量不提供另外疗效而伴随不良反应发生率增加。 2）通常注入胸锁乳突肌，头夹肌，肩胛提肌，斜角肌，和/或斜方肌。 3）剂量，数量，和注射部位的位置应根据涉及肌肉的数量和位置，肌张力失常的严重程度和对任何既往肉毒毒素注射的反应。 眼睑痉挛 (2.2) 1）当开始XEOMIN治疗，剂量，数量和注射位置应根据既往给予onabotulinumtoxinA(Botox)。XEOMIN对眼睑痉挛临床试验中，XEOMIN没有给予既往未曾接受过肉毒毒素型A[onabotulinumtoxinA](Botox)患者。 2）如既往肉毒毒素型A[onabotulinumtoxinA](Botox)剂量不知道，推荐起始剂量是1.25-2.5 单位每注射部位。 3）    在XEOMIN临床试验中，每个注射部位的平均剂量是5.6 单位，每只眼平均注射数为6,和每只眼平均剂量为33.5 单位. 剂型和规格 1）50单位，在单次用小瓶中冻干粉(3) 2）100单位，在单次用小瓶中冻干粉(3) 禁忌证 1）对活性物质肉毒神经毒素类型A或任何赋形剂超敏性 (4.1) 2）建议注射部位的感染 (4.2) 警告和注意事项 一般 1）XEOMIN的效力单位不能与其它肉毒毒素产品制品不能互换。所以，XEOMIN的生物活性单位不能与任何其它肉毒毒素产品比较或转换至其它产品单位 (5.1). 2）    毒性效应的播散可能引起吞咽和呼吸困难，可导致死亡(5.2). 3）呼吸，讲话或吞咽困难可能需要立即就医(5.2, 5.4). 4）在呼吸功能受损或吞咽困难患者慎用 (5.4). 5）同时神经肌肉疾患可能加重治疗的临床效应 (5.5). 颈部肌张力失常 (5.4) 1）有较小颈肌肉块患者和需要双侧注射至胸锁乳突肌患者是处于吞咽困难风险。 2）限制注入至胸锁乳突肌剂量可能减低吞咽困难的发生。 眼睑痉挛 (5.6) 1）角膜暴露和溃疡(5.6) 2）XEOMIN注入眼轮匝肌可能导致眨眼减少和角膜暴露与溃疡或穿孔可能性。 3）如用既往肉毒毒素注射发生复视不应重复下眼睑注射。 不良反应 颈部肌张力失常：最常观察到不良反应 (≥5%患者和>安慰剂)是：吞咽困难, 颈痛, 肌肉软弱, 注射部位痛,和肌肉骨骼痛(6.1)。 眼睑痉挛：最常观察到不良反应(≥5%患者和>安慰剂)是：眼瞼下垂，干眼，口干，腹泻，头痛，视觉障碍，呼吸困难，鼻咽炎，和呼吸道感染(6.1). 为报告怀疑的不良反应，联系Merz Pharmaceuticals, LLC公司(电话888-493-6646和http://www.merzusa.com)或FDA电话1-800-FDA-1088或www.fda.gov/medwatch. 药物相互作用 XEOMIN和氨基糖甙类抗菌素，奇放线菌素[spectinomycin]，或其它干扰神经肌肉传导药物(如，筒简毒样药物)，或肌肉松弛剂同时治疗时，应被严密观察因为XEOMIN的效应可能被加强(7). 在特殊人群中使用 1）妊娠：根据动物资料，可能引起胎儿危害 (8.1) 2）儿童使用：未曾在儿童年龄组中研究XEOMIN和所以不建议在儿童患者中使用 (8.4). INDICATIONS XEOMIN® is a prescription medicine that is injected into muscles and used: •to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in adults. •to treat abnormal spasm of the eyelids (blepharospasm) in adults who have had prior treatment with onabotulinumtoxinA (Botox®). •to temporarily improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) in adults. IMPORTANT SAFETY INFORMATION XEOMIN® may cause serious side effects that can be life threatening. Call your doctor or get medical help right away if you have any of these problems any time (hours to weeks) after treatment with XEOMIN: •Problems with swallowing, speaking, or breathing can happen after an injection of XEOMIN if the muscles that you use to breathe and swallow become weak. If these problems are severe, you could die. People with certain breathing problems may need to use muscles in their neck to help them breathe and may be at greater risk for serious breathing problems with XEOMIN. •Swallowing problems may last for several months, and during that time you may need a feeding tube to receive food and water. If swallowing problems are severe, food or liquids may go into your lungs. People who already have swallowing or breathing problems before receiving XEOMIN have the highest risk of getting these problems. •Spread of toxin effects. In some cases, the effect of botulinum toxin may affect areas of the body away from the injection site and cause symptoms of a serious condition called botulism. The symptoms of botulism include: loss of strength and muscle weakness all over the body, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing. Do not take XEOMIN if you: are allergic to XEOMIN or any of the ingredients in XEOMIN; had an allergic reaction to any other botulinum toxin product such as rimabotulinumtoxinB (Myobloc®), onabotulinumtoxinA (Botox®, Botox® Cosmetic), or abobotulinumtoxinA (Dysport®); have a skin infection at the planned injection site. Before you take XEOMIN, tell your doctor about all your medical conditions, including if you have a disease that affects your muscles and nerves (such as amyotrophic lateral sclerosis [ALS or Lou Gehrig’s disease], myasthenia gravis or Lambert-Eaton syndrome), as you may be at increased risk of serious side effects including difficulty swallowing or breathing. Tell your doctor if you have: had any side effect from any other botulinum toxin in the past; breathing problems such as asthma or emphysema; a history of swallowing problems or inhaling food or fluid into your lungs (aspiration); bleeding problems; drooping eyelids; plans to have surgery; had surgery on your face. Also tell your doctor if you are pregnant or plan to become pregnant (it is not known if XEOMIN can harm your unborn baby); are breastfeeding or plan to breastfeed (it is not known if XEOMIN passes into breast milk). Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal products. Using XEOMIN with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you have received XEOMIN in the past. Especially tell your doctor if you have received any other botulinum toxin product in the last four months or in the past. Be sure your doctor knows exactly which product you received. The dose of XEOMIN may be different from other botulinum toxin products that you have received. Tell your doctor if you: have recently received an antibiotic by injection; take muscle relaxants; take an allergy or cold medicine; take a sleep medicine; take a blood thinner medicine. XEOMIN may cause loss of strength or general muscle weakness, blurred vision, or drooping eyelids within hours to weeks of taking XEOMIN. If this happens, do not drive a car, operate machinery, or do other dangerous activities. XEOMIN may cause other serious side effects including allergic reactions. Symptoms of an allergic reaction to XEOMIN may include: itching, rash, redness, swelling, wheezing, asthma symptoms, or dizziness or feeling faint. Tell your doctor or get medical help right away if you get wheezing or asthma symptoms, or if you get dizzy or faint. Other side effects of XEOMIN include: dry mouth, discomfort or pain at the injection site, tiredness, neck pain, muscle weakness, and eye problems, including double vision, blurred vision, drooping eyelids, swelling of your eyelids, and dry eyes. Reduced blinking can also occur. Tell your doctor or get medical help right away if you have eye pain or irritation following treatment. 完整使用资料附件：http://www.drugs.com/pro/xeomin.html