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 详细处方信息以本药内容附件PDF文件（20124522065132.PDF,20124522054715.PDF,20124522053132.PDF）的“原文Priscribing Information”为准
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部分中文Zypadhera处方资料（仅供参考）

CHMP批荐批准奥氮平长效注射剂Zypadhera
    礼来公司近日表示欧洲人用药委员会(CHMP)已批荐批准奥氮平长效注射剂（Olanzapine Long-acting Injection (LAI)）用于作为成人精神分裂症患者的维持疗法，在欧洲的商品名将为Zypadhera。
    Olanzapine LAI为一种创新的奥氮平制剂，结合了帕莫酸盐持续释放时间达可达4周。在10月初该药在新西兰获得上市批准。目前该药正在美国、加拿大、澳大利亚及其它国家申请上市。

丹麦批准对ZypAdhera予以补贴
    丹麦医药管理局已批准给予Lilly公司的精神分裂症治疗药ZypAdhera（olanzaipine pamoate monohydrate，双羟萘酸奥氮平单水合物）一般性补偿，该药是规格为210、300和405mg的粉剂，供混悬剂用。此药已于去年获欧盟批准。但该机构拒绝批准给予第一三共公司用于治疗急性冠脉综合征、心肌梗死和全身性血栓形成的Efient（prasugrel）补贴。

OLANZAPINE奥氮平
<<商品名>>
台湾
健保药品 - Nodoff 纳得复膜衣锭 , Okpine 思克明膜衣锭 , Olandus 欧乐平膜衣锭 , Zyprexa 金普萨膜衣锭.
美国-  ZyPREXA;; ZyPREXA Relprevv; ZyPREXA Zydis
加拿大 -  Apo-Olanzapine; PHL-Olanzapine ODT; PMS-Olanzapine; PMS-Olanzapine ODT; Riva-Olanzapine ODT; Sandoz-Olanzapine ODT; Teva-Olanzapine OD; Zyprexa; Zyprexa Zydis
Zypadhera (捷克 , 德国, 丹麦, 法国,  爱尔兰, 荷兰,挪威, 葡萄牙, 瑞典);
Zyprexa (阿根廷, 奥地利,澳大利亚, 比利时, 巴西,瑞士, 智利, 德国, 丹麦, 西班牙,  芬兰, 法国,  希腊, 香港,印尼, 爱尔兰, 以色列,义大利,马利,  马尔他,  墨西哥, 马来西亚,  荷兰,挪威, 纽西兰) 秘鲁, 菲律宾, 巴基斯坦, 波兰, 葡萄牙, 俄罗斯, 瑞典, 新加坡, 斯洛伐克, 泰国, 土耳其, 委内瑞拉, 南非); Zyprexa Velotab (奥地利,比利时,瑞士, 德国, 丹麦, 西班牙, 芬兰, 法国,  希腊, 爱尔兰, 义大利,马尔他, 荷兰,挪威, 波兰, 葡萄牙, 俄罗斯, 瑞典, 斯洛伐克, 土耳其); Zyprexa Zydis (阿根廷, 香港,印尼, 马来西亚, 纽西兰) 新加坡, 泰国)

<<药物作用>
     Olanzapine 为第二代『非典型』精神病药物，主要用於精神分裂症及其它明显有正性及/或负性之精神病，双极性疾患之躁期发作，预防双极性疾患之复发。它也可与锂盐(Lithium) 或valproic acid合并使用以控制躁郁症。除了产品标签所核准精神分裂适应症外、非典型精神病药物常被医师广泛的运用到治疗焦虑症、强迫症等。
     非典型精神病药物的作用机制与大多数精神药物一般，仍然未知、但相信它们主要作用於脑部神经传导物质多巴胺(Dopamine)或血清素(Serotonine) 的感受器官而产生疗效。相较『传统』的抗精神药物，『非典型』抗精神病较不会引起明显的锥体外径副作用。『非典型』抗精神病药除了可以改善精神分裂症的正性症状如幻觉、妄想、行为怪异及语无伦次等，对於负性症状如社交退缩、缺乏逻辑、情绪冷漠、兴趣缺乏等也具有疗效。

<<用法>>
     Olanzapine 通常一天服用一次，空腹或与食物并用均可。由於药物具有镇静安眠的特性，如果一天服药一次、最好安排在睡前使用、不论是早上或是晚上服用，最好养成每天在固定时间服药的良好习惯，以避免忘记服药。。当开始服药，尤其在前几个星期的治疗期间，医生会依个人的临床症状，使用较低剂量并逐步增加剂量以降低副作用的可能，待稳定後再保持每日维持剂量，病患应该依照医师指示服用。在服用药物之前，如果有不了解的部分，应该要求医师或药师做详细的解释。此药的药效通常需2至4周才会发生作用，病患应遵循医师指示服药、在未经医师许可前，不可自行停药。

<<注意事项>>
     如果怀孕，对药物过敏，帕金森症、心绞痛、心跳不规则，肝脏疾病，药物濫用、脑中风、癫痫发作，青光眼等，医师需要针对这些情况谨慎用药，因此在使用此药前，应该事先通知医师。
     Olanzapine可能使体内血糖浓度增高、导致糖尿病及其它并发症的发生。身体过於度肥胖及有糖尿病家族史的病患、发生的机率最大。病患在使用药期间应该定期测量血糖、常运动及保持适当体重、并随时留意糖尿病可能症状如：容易饥饿和口渴、感觉疲劳  视力减弱、尿频等。若出现高血糖症状时应立即测量血糖值。假若在危急情况下、应该立即通知医师。
    美药管局(FDA)曾发出警讯指出、使用『非典型』精神病药物可能会使老年痴呆症患者带来严重不良反应。根据临床结果显示、患有老年痴呆的年长精神病患在使用『非典型』精神病药物的死亡率(4.5%)较使用安慰剂的对照组(2.6%)高出约1.6倍。通报并指出虽然病患的死因不同、但大多与心脏疾病或细菌感染有关、死亡率的增加是否与精神药物的使用或病患具有的某些特性有关、还无法进一步的确定。
     所有抗精神病药物包括Olanzapine可能发生极罕见、有潜在致死性的复合症状群,称为『抗精神病药恶性症状群(NMS)』此一副作用发生的机率极为低、但与药物的剂量及使用时间长短无关、任何服药期间都可能发生、但以最初用药的三十天内发生机率最高。NMS主要症状为心跳速率增快或失常、肌肉无力、肌肉痛、肌肉僵硬、血压不稳、呼吸急促，冒汗、脉博不规律、发高烧、精神状态改变、颤抖、横纹肌溶解进而产生肾衰竭等。如果有以上症状发生、应该立即通知医师
     使用抗精神类药物较需考虑的副作用是药物所引起的锥体外径症状。虽然『非典型』抗精神病药不同於『传统』的抗精神药物，比较不会引起锥体外径副作用、但是病患在服药期间仍需留意服药後的反应、如有症状发生、应该咨询医师的意见。常见锥体外径症状为无法控制地眨眼睛、手臂或双腿有抖动的现象、舌头经常往外突出、嘴巴歪斜、眼球上吊、颈向後仰，无法克制想起来走动的感觉。
     此药只能用来控制病情，但不能治愈病症。经过一阵子服药後，即使感觉病情稳定，仍需继续服药，更不可随意停药。突然停药可能使病况转坏或再次发作，同时也可能产生恶心，呕吐，失眠或昏睡等戒断症状。如有必要停药时，医师通常会逐渐减少药量，然後再停。
     此药可能会让您觉得眩晕或嗜睡，除非已经适应了此药的作用，当开车或操作危险机械时，应该格外小心谨慎。如果感觉眩晕，缓慢站立成坐起，应该会减少此一现象。酒精会增加此药嗜睡的副作用，应当避免或限制酒量。
     此药会降低身体排汗及散热的能力。因此，应该避免在阳光下及过热的地方站立太久、以免中暑;同时，洗澡时也应该避免水温太热、散热不良及血压下降而造成晕倒。
     此药可能会造成姿态性低血压症，这是由於病人由平躺的姿势突然改为直立时，由於血压迅速降低且无法在短时间提升造成头昏目眩，视力模糊，虚弱、甚至昏厥等不适症状。这种现象通常在最初给药的3-5天以及剂量调整期间最常发生，对於平常血压过低的病人，刚开始服药时应该特别小心，不过如果能够缓慢地站立或坐起，应该会减少此一现象。

<<怀孕及哺乳>>
     美国药管局(FDA)将此药归类为怀孕类别C级：C级表示动物繁殖研究显示药物对胎儿有不利影响、但没有对人类孕妇所做对照组研究。尽管有潜在风险、但在潜在利益大於潜在危险前提下、仍然可以考虑使用。
     在动物繁殖研究中、分别使用9和30倍的最大人类推荐下、没有证据指出会引起动物胎儿的致畸性。怀孕最後三个月使用药物有可能使新生儿产生可逆的锥体外症候群或戒断症状。此症状包括情绪激动、喂哺困难、肌张力亢进、张力减退、呼吸困难、嗜睡和颤抖等、这些影响可能会自行康复或需要住院治疗。此药对人类孕妇没有足够和良好对照的研究、如果怀孕就应该通知医师。除了用药的优点胜於对胎儿的危险性，并且经过医师的许可外，孕妇应该避免服用此药。
     妇女使用精神药物期间如果发现怀孕。在医师评估病情及许可前、不该自行停止服药。
     Olanzapine会经由母乳排出、约有2%的剂量会经由母乳吸收入婴儿体内。喂奶的母亲在使用此药时，应该停止喂食母乳，而改用其他的乳制品取代。

<<副作用>>
     食欲增加（3％至24％）、便秘（4％至11％）、口乾（3％至32％）。其它可能副作用包括：头晕、躁动、抑郁、失眠、手脚疼痛、关节疼痛、乳房胀大或分泌、月经周期改变、性能力下降、体重增加、胃不舒服、焦虑不安、发抖，困倦、便秘或腹泻、呕吐、头痛等。这些副作用，通常在服用药物一阵子後，应该会渐渐消失。如果这些副作用强到困扰你的程度，或者经过一段时间後，这些症状还不能完全消除，就应该通知医师。
     此药较严重的副作用为: 大量流汗、心跳加速或不规则、视觉变化、手脚肿胀、喉咙痛、肌肉僵硬、吞咽困难、排尿困难、发烧或其他感染迹象、皮肤起皮疹或荨麻疹、呼吸困难、无法站立、无法控制的痉挛动作等。通常这些副作用发生的机率较低，但是如果发生时，此可能是药物造成的不良反应，或者是剂量需要调整，应该尽快通知医师。

<<忘记用药>>
     如果忘记服药，应该在记得时，立即服用。但是，如果距离下次服药的时间太近，就应该舍弃所遗忘的药物，恢复到下次正常服药的时间，千万不可一次服用双倍的剂量。

What is Zypadhera?
Zypadhera is a powder and solvent that are made up into a prolonged-release suspension for injection. It contains the active substance olanzapine. ‘Prolonged release’ means that the active substance is released slowly over a few weeks after being injected.

What is Zypadhera used for?
Zypadhera is used to maintain the improvement in symptoms in patients with schizophrenia who have already been stabilised on an initial course of olanzapine taken by mouth. Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (false beliefs).

The medicine can only be obtained with a prescription.

How is Zypadhera used?
Zypadhera is given by deep injection into the buttock muscle by a doctor or nurse who has been trained in giving this type of injection. In rare cases, patients receiving Zypadhera may experience symptoms of olanzapine overdose after injection if the medicine is accidentally injected into a vein. Symptoms of overdose include sedation (sleepiness) and delirium (confusion). Because patients should be monitored by qualified staff for these symptoms for at least three hours after injection, they should receive Zypadhera at a centre with the appropriate facilities to deal with a potential overdose. Patients who have symptoms of overdose should continue to be monitored until the symptoms have passed. Zypadhera must not be injected into a vein or under the skin.

Zypadhera is given at doses of 150, 210 or 300 mg every two weeks, or 300 or 405 mg every four weeks. The dose depends on the dose of olanzapine that the patient was previously taking by mouth. Patients should be monitored closely for signs of relapse (a return of symptoms) during the first one to two months of treatment, and the dose adjusted if necessary.

Zypadhera is not recommended for patients over 65 years of age. However, patients aged between 65 and 75 years or patients with kidney or liver problems may use Zypadhera if an effective and well-tolerated dose of oral olanzapine has been found. A lower starting dose may be necessary in patients whose bodies may break olanzapine down slowly, such as those with moderate liver problems.

How does Zypadhera work?
The active substance in Zypadhera, olanzapine, is an antipsychotic medicine. It is known as an ‘atypical’ antipsychotic because it is different from the older antipsychotic medicines that have been available since the 1950s. Olanzapine attaches to several different receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by ‘neurotransmitters’, chemicals that allow nerve cells to communicate with each other. It is thought that olanzapine’s beneficial effect is due to it blocking receptors for the neurotransmitters 5-hydroxytrypamine (also called serotonin) and dopamine. Since these neurotransmitters are involved in schizophrenia, olanzapine helps to normalise the activity of the brain, reducing the symptoms of the disease.

Olanzapine has been authorised in the European Union (EU) since 1996. It is available as tablets, orodispersible tablets (tablets that dissolve in the mouth) and rapidly acting injections in Zyprexa, Zyprexa Velotab and other medicines. The olanzapine in Zypadhera is presented as a ‘pamoate’ salt, which makes the olanzapine less soluble. As a result, the active substance is released slowly for more than four weeks after injection of Zypadhera.

How has Zypadhera been studied?
Because olanzapine has already been authorised in the EU as Zyprexa, the company used some of the data from Zyprexa to support the use of Zypadhera.

Zypadhera has been studied in two main studies involving adults with schizophrenia. The first looked at the initial treatment of schizophrenia and the second looked at the maintenance of response to olanzapine treatment:
the study of initial treatment compared the effects of three doses of Zypadhera with those of placebo (dummy injections) in 404 patients. The main measure of effectiveness was the change in symptoms measured on a standard scale for schizophrenia after eight weeks;
the study of maintenance treatment compared the effects of four doses of Zypadhera with those of olanzapine taken by mouth in 1,065 patients. Three of the doses of Zypadhera were ‘high’ (300 mg and 150 mg every two weeks, and 405 mg every four weeks) and one was ‘low’ (45 mg every four weeks). All of the patients in this study had been stabilised with other treatments for schizophrenia and had been taking olanzapine by mouth for at least six weeks before the study began. The main measures of effectiveness were the time taken for symptoms to get worse and the number of patients whose symptoms got worse over 24 weeks.

What benefit has Zypadhera shown during the studies
In the study of the initial treatment of schizophrenia, Zypadhera was more effective than placebo. Symptom scores were around 100 points at the start of the study, but had fallen by around 25 points in the patients receiving Zypadhera after eight weeks, compared with around 9 points in the patients receiving placebo. The effectiveness of Zypadhera was greater than placebo from the second week of treatment onwards.

In the study looking at the maintenance of response to olanzapine treatment, Zypadhera was as effective as olanzapine taken by mouth: 10% of the patients receiving Zypadhera every two weeks had a worsening of symptoms, compared with 7% of those taking olanzapine by mouth. The ‘high’ doses of Zypadhera were more effective at preventing a worsening of symptoms than the ‘low’ dose.

What is the risk associated with Zypadhera?
The most common side effects with Zypadhera (seen in more than 1 patient in 10) are weight gain, somnolence (sleepiness) and raised levels of prolactin (a hormone). For the full list of all side effects reported with Zypadhera, see the Package Leaflet.

Zypadhera should not be used in patients who may be hypersensitive (allergic) to olanzapine or any of the other ingredients. It must not be used in patients at risk of narrow-angle glaucoma (raised pressure inside the eye).

Why has Zypadhera been approved?
The Committee for Medicinal Products for Human Use (CHMP) noted that Zypadhera is effective both in the initial treatment of schizophrenia and in maintaining a response to treatment in schizophrenia. However, it noted that prolonged-release injections are not suitable for use as initial treatment, because the medicine takes at least a week to reduce symptoms and patients may need rapid control of symptoms. In addition, it is not possible to stop treatment after giving a prolonged-release injection, which would not be suitable for patients experiencing side effects. Therefore, the Committee decided that Zypadhera’s benefits are greater than its risks for maintenance treatment of adult patients with schizophrenia sufficiently stabilised during acute treatment with oral olanzapine. The Committee recommended that Zypadhera be given marketing authorisation.

Which measures are being taken to ensure the safe use of Zypadhera?
The company that makes Zypadhera will provide an educational programme for doctors, nurses and pharmacists and a card for patients in all Member States, reminding them of how to use the medicine safely. These will include information on what to do before and after each injection, the differences between Zypadhera and other injectable medicines containing olanzapine, and the recommendations on how patients should be monitored.

Other information about Zypadhera
The European Commission granted a marketing authorisation valid throughout the EU for Zypadhera to Eli Lilly Nederland BV on 19 November 2008.

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 详细处方信息以本药内容附件PDF文件（20124522065132.PDF,20124522054715.PDF,20124522053132.PDF）的“原文Priscribing Information”为准
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