Pfizer公司8月23日宣称，FDA已批准他们的非经典抗精神病药物Geodon用来治疗急性双极躁狂症。在一项随机、双盲临床试验中，选择了416名入院的急性双极躁狂症患者。经Geodon治疗后，患者从第二天到治疗结束时的第21天与安慰剂相比，症状均有明显缓解。Geodon的开始剂量最80mg／d、第二天可以增加到160mg／d。

研究中，Geodon的常见副作用是嗜睡、头晕和锥体外束的症状。它不生增加病人如体重。而这正是其它治疗药物的一个令人头疼的副作用。以往许多患者因为体重增加而拒绝服用药物。Geodon疗效显著，又没有这一副作用，或许可以被这类患者接受。

【药品名称】盐酸齐拉西酮胶囊

【英文名】Ziprasidone Hydrochloride Capsules

【化学名】5-[2-[4-(1,2-苯并异噻唑-3-基)-1-哌嗪基]乙基]-6-氯-1,3-二氢-2(1H)-吲哚-2-酮盐酸盐半水合物。

【分子式】C21H21ClN4OS·HCl·1/2H2O

【分子量】458.41

【性状】本品为硬胶囊，内容物为白色至微红色颗粒或粉末。

【药理毒理】
药理作用:
齐拉西酮是一种非典型抗精神病药，其结构与吩噻嗪类或丁酰苯类抗精神病药物不同。体外研究显示，齐拉西酮对多巴胺D2、D3、5-羟色胺5HT2A、5HT2C、5HT1A、5HT1D和α1-肾上腺素能受体具有较高的亲和力，对组胺H1受体具有中等亲和力，对包括M胆碱能受体在内的其他受试受体/结合位点未见亲和力。齐拉西酮对D2、5HT2A、5HT1D受体具有拮抗作用，对5HT1A受体具有激动作用。齐拉西酮能抑制突触对5-羟色胺和去甲肾上腺素的再摄取。
与其他抗精神分裂症药物一致，齐拉西酮的作用机制不明确。研究认为其抗精神分裂症作用可能是通过对D2和5HT2受体的拮抗作用来发挥的，对其他相似亲和力受体的拮抗作用可能是导致其他治疗作用和副作用的原因。对H1受体的拮抗作用可能是齐拉西酮产生嗜睡的原因，对α1-肾上腺素能受体的拮抗作用可能是产生体位性低血压的原因。
毒理研究:
遗传毒性 Ames试验中，在无代谢活化时齐拉西酮可使一株鼠伤寒沙门氏菌回复突变率升高。小鼠淋巴瘤细胞基因突变试验、人淋巴细胞染色体畸变试验结果均为阳性，小鼠微核试验结果为阴性。
生殖毒性 SD大鼠在齐拉西酮剂量为10~160mg/kg/天(按mg/m2推算，相当于人最大推荐剂量200mg/天的0.5~8倍)时可见交配时间延长，在剂量为160mg/kg/天时生育力降低，在剂量为40mg/kg/天时对生育力未见影响。雄性大鼠在剂量为160mg/kg/天时与未给药雌性大鼠交配后，未见生育力降低，因此齐拉西酮可能仅对雌性大鼠的生育力有影响。在一项周期为6个月的大鼠试验中，给药剂量为200mg/kg(按mg/m2推算，相当于人最大推荐剂量200mg/天的10倍)，未见对睾丸的影响。
大鼠致畸敏感期给予齐拉西酮10~160mg/kg/天，可见胎仔体重降低、骨骼骨化延迟，但未见畸形，对发育无影响剂量为5mg/kg/天。在剂量为40和160mg/kg时可见母体毒性。家兔致畸敏感期给予齐拉西酮30mg/kg/天(按mg/m2推算，相当于人最大推荐剂量200mg/天的3倍)可见胎仔结构畸形发生率增加，对发育无影响剂量为10mg/kg/天。
大鼠围产期给予齐拉西酮10mg/kg/天(按mg/m2推算，相当于人最大推荐剂量200mg/天的0.5倍)或更高剂量，死产数增加，哺乳前4天存活动物数减少。在剂量为5mg/kg/天(按mg/m2推算，相当于人最大推荐剂量200mg/天的0.2倍)时，可见子代动物发育延迟和神经行为功能受损。
致癌性 Long Evans大鼠和CD-1小鼠掺食法分别给予齐拉西酮2、6、12mg/kg/天或50、100、200mg/kg/天(按mg/m2推算，分别相当于人最大剂量200mg/天的0.1~0.6倍和1~5倍)，连续24个月。与对照组比较，大鼠和雄性小鼠中未见肿瘤发生率增加。在雌性小鼠中，可见垂体腺瘤和垂体癌、乳腺癌发生率呈剂量依赖性增加。啮齿类动物长期给予其他抗精神病药物可见垂体和乳腺增生，认为是催乳素介导的。小鼠掺食法给予齐拉西酮100、200mg/kg/天，连续1个月，可见雌性小鼠血清催乳素水平升高，雄性小鼠无影响。大鼠掺食法给予齐拉西酮也未见催乳素改变。啮齿类动物中催乳素介导的内分泌肿瘤对人体用药风险的相关性尚不明确。

【药代动力学】
齐拉西酮的药理活性主要来自原形，口服盐酸齐拉西酮后经胃肠道吸收良好，分布广泛，6-8小时达血浆峰浓度，1-3天达到稳态血浓度，血浆蛋白结合率大于99%，表观分布容积为1.5L/kg，餐时服用20mg的绝对生物利用度约为60%，食物能增加本品的吸收约2倍。平均终末半衰期(T1/2)约为7小时，平均表观系统清除率为7.5mL/min/kg。血浆蛋白结合率大于99%。口服齐拉西酮后主要经肝脏充分代谢，仅少量原形药经尿液(＜1%)和类便(＜4%)排泄。齐拉西酮主要经三种代谢途径消除、生成四种主要可循环代谢产物:苯并异噻唑(BITP)亚砜，BITP-砜，齐拉西酮亚砜和S-甲基-二氢齐拉西酮。经尿液和粪便排泄的药物分别约为20%和66%，血清中原形齐拉西酮约为44%。离体人肝细胞组份研究表明，经两步生成S-甲基-二氢齐拉西酮。离体人肝微粒体和重组酶研究表明，氧化代谢齐拉西酮的CYP酶主要是CYP 3A4，CYP1A2的作用较弱。在体内分泌和代谢资料表明，低于1/3的齐拉西酮经细胞色素P450氧化代谢消除，约2/3齐拉西酮经醛氧化酶代谢清除。对醛氧化酶有临床意义的抑制剂或激动剂情况尚不清楚。
年龄、性别和种族对齐拉西酮药代动力学无影响。不需据此调整剂量。
烟:群体药代动力学研究表明，吸烟和不吸烟对齐拉西酮的药代动力学无影响。
肾损伤:齐拉西酮代谢率高，经肾分泌的原形药物低于1%，单独肾损伤对齐拉西酮的药代动力学无明显影响，不需根据肾功能损伤程度调整用药剂量。
肝损伤:齐拉西酮主要经肝脏清除，肝损伤导致齐拉西酮AUC增加。

【适应症】
本品适用于治疗精神分裂症。

【用法用量】
初始治疗:一次20mg，一日二次，餐时口服。视病情可逐渐增加到一次80mg、一日二次。为了确保最低有效剂量，在调整剂量前应仔细观察患者用药后的反应。剂量调整间隔一般应不少于2天，因为口服本品在1-3天内血药浓度达到稳定状态。
维持治疗:应定期评估并确定患者是否需维持治疗。尽管齐拉西酮维持治疗的时间长短尚未确定，但在52周临床试验中，精神分裂症患者持续使用齐拉西酮的有效剂量为:一次20-80mg，一日二次；一次大于20mg以上(一日二次)齐拉西酮未证实有其他益处。
特殊人群用药:不同年龄、性别、种族人群，以及肾功能或者肝功能损伤的患者，一般均均无需调整剂量。

【不良反应】
国外上市前临床试验报道了以下不良反应:
精神分裂症患者:齐拉西酮组和安慰剂组不良反应所致停药率分别为4.1%(29/702)和2.2%(6/273)。主要不良反应为皮疹，齐拉西酮组为1%，安慰剂组为0。短期安慰剂对照试验中，发生率大于5%的常见不良反应见下表。

Geodon(Ziprasidone) 40mg

Generic Name: ziprasidone (zi PRAY si done)
Brand Names: Geodon

What is Geodon?
Geodon (ziprasidone) is an antipsychotic medication. It works by changing the effects of chemicals in the brain.

Geodon is used to treat schizophrenia and the manic symptoms of bipolar disorder (manic depression) in adults and children who are at least 10 years old.

Geodon may also be used for other purposes not listed in this medication guide.

Important information about Geodon
Geodon is not for use in psychotic conditions related to dementia. Geodon may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

Do not use Geodon if you have a personal or family history of "Long QT syndrome," if you have recently had a heart attack, or if you have uncontrolled heart failure.

Stop taking Geodon and call your doctor right away if you feel dizzy or light-headed, have a fast or pounding heartbeat, or if you faint. This could be signs of a serious heart rhythm problem.

There are many other medicines that can cause serious or life-threatening medical problems if you take them together with Geodon. 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. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Before taking Geodon
Geodon is not for use in psychotic conditions related to dementia. Geodon may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions. Do not use this medication if you are allergic to ziprasidone, or if you have:
a personal or family history of "Long QT syndrome";
history of recent heart attack; or
uncontrolled or untreated heart failure.

Geodon should never be taken together with any of the following drugs, or a life-threatening heart rhythm disorder could occur:
arsenic trioxide (Trisenox);
dolasetron (Anzemet);
droperidol (Inapsine);
halofantrine (Halfan);
mefloquine (Lariam);
levomethadyl acetate (no longer available in the U.S.);
tacrolimus (Prograf);
antibiotics such as gatifloxacin (Tequin), pentamidine (NebuPent, Pentam), moxifloxacin (Avelox), sparfloxacin (Zagam), telithromycin (Ketek);
heart rhythm medicine such as dofetilide (Tikosyn), disopyramide (Norpace), quinidine (Cardioquin, Quinaglute), or sotalol (Betapace); or
medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), mesoridazine (Serentil), pimozide (Orap), or thioridazine (Mellaril).

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take Geodon:
a heart rhythm disorder;
a history of heart attack or stroke;
a history of bone marrow or blood cell disorder;
low blood levels of potassium or magnesium;
diabetes (Geodon may raise your blood sugar);
seizures or epilepsy;
a history of suicidal thoughts;
Parkinson's disease, Alzheimer's;
trouble swallowing;
liver disease; or
kidney disease.

Geodon may cause you to have high blood sugar (hyperglycemia). Talk to your doctor if you have any signs of hyperglycemia such as increased thirst or urination, excessive hunger, or weakness. If you are diabetic, check your blood sugar levels on a regular basis while you are taking Geodon.

The orally disintegrating tablet may contain phenylalanine.

Talk to your doctor before using this form of Geodon if you have phenylketonuria (PKU).

FDA pregnancy category C. It is not known whether Geodon is harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether ziprasidone 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. Older adults may be more likely to have side effects from Geodon.

How should I take Geodon?
Take Geodon exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

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

To be sure Geodon is not causing harmful effects, your blood will need to be tested on a regular basis. Your kidney or liver function may also need to be tested. Do not miss any scheduled appointments.

Take this medicine with food.

It is important to take Geodon regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

It may take several weeks of using this medicine before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve. Store Geodon at room temperature away from moisture, light, and heat.

What happens if I miss a dose?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?
Seek emergency medical treatment if you think you have used too much of this medicine. Overdose symptoms may include drowsiness, problems with speech, dizziness, feeling light-headed, fainting, fast or pounding heartbeat, or restless muscle movements in your eyes, tongue, jaw, or neck.

What should I avoid while taking Geodon?
While you are taking Geodon, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking this medicine. Geodon can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of Geodon.

Geodon side effects
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. Stop using Geodon and call your doctor at once if you have any of these serious side effects:
dizziness, feeling light-headed, fainting, fast or pounding heartbeat;
stiff muscles, confusion, sweating, fast or uneven heartbeats;
fever, chills, body aches, flu symptoms;
white patches or sores inside your mouth or on your lips;
tremor (uncontrolled shaking), restless muscle movements in your eyes, tongue, jaw, or neck;
agitation, hostility, confusion;
increased thirst or urination, weakness, extreme hunger; or
penis erection that is painful or lasts 4 hours or longer.

Less serious Geodon side effects may include:
mild skin rash;
anxiety, headache, depressed mood;
dizziness, drowsiness;
muscle pain or twitching;
nausea, vomiting, loss of appetite;
runny or stuffy nose, cough, sore throat; or
weight gain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Geodon?
Before taking Geodon, tell your doctor if you regularly use any other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by Geodon.

Tell your doctor about all other medications you are using, especially:
a diuretic (water pill), blood pressure medicine, or heart rhythm medicine;
carbamazepine (Carbatrol, Tegretol);
cisapride (Propulsid);
haloperidol (Haldol);
narcotic pain medication;
medicines used to treat Parkinson's Disease such as levodopa (Dopar, Larodopa, Sinemet, Atamet, others); or
antibiotics such as azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin (E-Mycin, E.E.S., Erythrocin, Ery-Tab), ketoconazole (Nizoral), or telithromycin (Ketek).

This list is not complete and there may be other drugs that can interact with Geodon. 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 Geodon.

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.

【-原产地英文商品名-】GEODON 40mg/cap 60caps/box
【-原产地英文药品名-】ZIPRASIDONE HCL
【-中文参考商品名-】GEODON 40毫克/胶囊 60胶囊/盒
【-中文参考药品名-】盐酸齐拉西酮
【-中文参考化合物名称-】5-[2-[4-(1,2-苯并异噻唑-3-基)-1-哌嗪基]乙基]-6-氯-1,3-二氢-2(1H)-吲哚-2-酮盐酸盐半水合物
【-临床试验期-】完成
【-中文适应病症参考-】急性双极躁狂症
【-中文适应病症参考-】抗精神病
【-中文适应病症参考-】抗焦虑
【-中文适应病症参考-】精神分裂症
【-生产厂家中文参考名-】辉瑞
【-生产厂家英文名-】PFIZER