近日，美国FDA批准礼来公司开发的复方奥氮平（olanzapine）/盐酸氟西汀(fluoxetine HCl)胶囊（商品名：Symbyax）上市，用于治疗双相性精神障碍引起的抑郁发病。
批准日期：2003年12月24日 公司：礼来公司
SYMBYAX（奥氮平和氟西汀）胶囊口服使用
美国首次批准：2003
警告：
自杀念头和行为;死亡率增加老年痴呆相关精神病查看完整的黑框警告完整的处方信息。
自杀想法和行为对儿童，青少年和年轻的成年人服用抗抑郁药的风险增加。 SYMBYAX没有在孩子不到10岁 批准使用。
监测恶化，自杀念头和行为出现。
老年痴呆患者的相关精神病用抗精神病药物治疗是在死亡的风险增加。 SYMBYAX未被批准用于治疗老年痴呆症相关的精神病的治疗。
目前的主要变化
警告和注意事项：
    代谢变化 12/2014
    闭角型青光眼 07/2014
    高泌乳素血症 12/2014
适应症和用法
SYMBYAX®结合奥氮平，非典型抗精神病药和氟西汀，选择性血清素再摄取抑制剂，用于治疗表明：
急性抑郁发作伴有双相I型
难治性抑郁症
用法用量
成人开始剂​​量：6毫克奥氮平25毫克氟西汀（6毫克/25毫克，每日一次在晚上.
成人最大剂量：12毫克/50毫克，每天一次（2.1,2.2）。
儿童双相抑郁的起始剂量：每天一次（10岁至17岁）3毫克/25毫克。
儿童双相抑郁最大剂量：12毫克/50毫克）
开始患者易患低血压反应，肝功能障碍的剂量，或具有潜在减缓代谢：3毫克/25毫克至6毫克/25毫克。升级剂量谨慎
剂型和规格
胶囊：3毫克/25毫克，6毫克/25毫克，6毫克/50毫克，12毫克/25毫克和12毫克/50毫克（毫克奥氮平/毫克当量氟西汀）
禁忌
单胺氧化酶抑制剂（MAOI）：由于血清素综合征的风险，不要使用单胺氧化抑制剂用于治疗精神障碍与SYMBYAX或5周SYMBYAX停止治疗的范围内。不要在一个停止MAOI用于治疗精神疾病的14天内使用SYMBYAX。此外，不要在谁是被利奈唑胺或静脉注射亚甲蓝治疗的患者开始SYMBYAX。
匹莫齐特：不要使用。 QT间期延长的风险.
硫利达嗪：不要使用。风险QT间期延长。不要5周停止SYMBYAX内使用硫利达嗪.
警告和注意事项
神经阻滞剂恶性综合征：用管理立即停止，并密切监测.
代谢变化：非典型抗精神病药物已与代谢的变化，包括高血糖症，血脂异常，和体重增加关联的
高血糖和糖尿病：在某些情况下，极端的酮症酸中毒或高渗性昏迷或死亡有关。监测血糖的症状。开始之前，和治疗期间定期执行空腹血糖测试。
血脂异常：适当的临床监测建议，包括开始之前空腹血脂检测，并定期期间，处理
体重增加：考虑体重增加的潜在后果。定期监测体重.
血清素综合症：血清素综合征已报告的SSRIs和SNRIs的，包括SYMBYAX，既当单独存在时，但特别是当共同给予与其他血清素剂（包括曲坦，三环抗抑郁药，芬太尼，锂，曲马多，色氨酸，丁螺环酮和圣金丝桃素）。如果出现这些症状，应停止SYMBYAX并开始支持治疗。如果同时使用SYMBYAX与其他血清素药物在临床上必要的，患者应该意识到潜在的风险增加血清素综合征，特别是在治疗开始和剂量的增加。
闭角型青光眼：闭角型青光眼患者发生与抗抑郁药治疗的解剖未经窄房角
过敏反应和皮疹：请停止在外观的皮疹或过敏现象
工坊/轻躁狂的激活：屏幕躁郁症和监测激活躁狂/轻躁狂
迟发性运动障碍：如果临床适当请停止
体位性低血压：可与心动过缓和晕厥有关。在初始剂量滴定风险增加。请谨慎患者心血管疾病或脑血管疾病，而这些条件可能影响血流动力学反应
白细胞减少，中性粒细胞减少，粒细胞缺乏和：有报道用抗精神病药物，包括SYMBYAX。患者的临床显著低白细胞计数的历史（WBC）或药物引起的白细胞减少/中性粒细胞减少应具有其全血细胞计数（CBC）经常监测在治疗的最初几个月。考虑停止SYMBYAX在白细胞中的临床显著下降，没有其他致病因素的第一个迹象
癫痫发作：患者谨慎使用有惊厥史或与降低癫痫发作阈值条件.
异常出血：SSRIs类药物增加出血的风险。使用NSAIDs的使用，阿司匹林，华法林，或影响凝血功能的药物发生增强胃肠道或其他出血的风险
低钠血症：可发生在抗利尿激素（SIADH）综合征关联。考虑停止症状，如果出现低钠血症SYMBYAX（SIADH）
潜在的认知和运动功能障碍：有潜力影响判断力，思维和运动技能。注意患者约作业机械.
QT延长：QT间期延长和室性心律失常，包括尖端扭转型室，已报告有氟西汀。在易患心律失常或氟西汀增加曝光条件请谨慎使用。患者慎用的危险因素QT间期延长.
高催乳素血症：可提高催乳素水平.
长期消除半衰期氟西汀：在改变剂量不会完全反映在等离子数周.
不良反应
最常见的不良反应（≥5％和至少两次，对安慰剂）成人：镇静，体重增加，食欲增加，口干，乏力，水肿，震颤，干扰注意力，视力模糊。儿童和青少年：镇静，体重增加，食欲增加，震颤，甘油三酯升高，肝酶升高.
药物相互作用
单胺氧化酶抑制剂（莫伊）：
药物被CYP2D6代谢：氟西汀是CYP2D6酶途径的有效抑制剂.
三环类抗抑郁药（TCAS）：联合用药期间监测TCA含量与SYMBYAX或者SYMBYAX最近已经停产.
中枢神经系统作用药物：注意建议如果需要SYMBYAX和其他中枢神经系统活性药物合用.
降压药：增强降压作用.
左旋多巴和多巴胺受体激动剂：可拮抗左旋多巴/多巴胺受体激动剂.
苯二氮类：可增强体位性低血压和镇静.
氯氮平：可以提高氯氮平水平.
氟哌啶醇：氟哌啶醇升高水平已观察到.
卡马西平：潜在高架卡马西平水平与临床抗惊厥毒性.
苯妥英钠：潜在高架苯妥英钠水平与临床抗惊厥毒性.
酒精：会增强镇静和体位性低血压.
血清素药品：
氟伏沙明：可能会增加奥氮平的水平;较低剂量SYMBYAX的奥氮平成分的，应考虑.
与止血干扰药物：（例如，的NSAIDs，阿司匹林，华法林等）：会增强的出血风险.
药物紧密与血浆蛋白结合：氟西汀可能导致移血浆浓度.
药物延长QT间期：组合不要使用SYMBYAX与硫利达嗪或匹莫齐特。使用SYMBYAX慎用与延长QT间期其他药物联合.
特殊人群中使用
怀孕：SYMBYAX应在怀孕期间使用只有在潜在的好处辩解潜在的风险对胎儿.
哺乳期妇女：哺乳，不建议.
儿童用药：Symbyax的安全性和有效性双相抑郁症我的病人在10岁以下的治疗尚未确定。安全Symbyax和有效性在18岁以下的患者难治性抑郁症还没有建立.
肝损伤：使用的肝硬化患者较低或较不频繁的剂量.
包装规格[注：以下是美国产品，采购者以咨询为准]
SYMBYAX CAP 6/50MG 30 OLANZAPINE/FLUOXETINE HCL  ELI LILLY AND COMPANY  00002-3233-30            
SYMBYAX CAP 12/25MG 30  OLANZAPINE/FLUOXETINE HCL  ELI LILLY AND COMPANY  00002-3232-30            
SYMBYAX CAP 6/25MG 30  OLANZAPINE/FLUOXETINE HCL  ELI LILLY AND COMPANY  00002-3231-30            
SYMBYAX CAP 3/25 30  OLANZAPINE/FLUOXETINE HCL  ELI LILLY AND COMPANY  00002-3230-30            
SYMBYAX CAP 12/50MG 30 OLANZAPINE/FLUOXETINE HCL  ELI LILLY AND COMPANY  00002-3234-30 
完整资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6b28c424-0b7e-4b75-b090-f116b113554e 
Symbyax
Generic Name: fluoxetine and olanzapine (floo OX eh teen and oh LAN za peen)
Brand Names: Symbyax
What is Symbyax?
Symbyax (fluoxetine and olanzapine) contains a combination of fluoxetine and olanzapine.
Fluoxetineisanantidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs).
Olanzapine is an antipsychotic medication. These drugs affect chemicals in the brain.
Symbyax is used to treat depression caused by bipolar disorder(manic depression). Symbyax is also used to treat depression after at least 2 other medications have been tried without successful treatment of symptoms.
Symbyax may also be used for other purposes not listed in this medication guide.
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Important information about Symbyax
Symbyax is not for use in psychotic conditions related to dementia. Symbyax may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions. Do not take Symbyax together with pimozide (Orap), thioridazine (Mellaril), or a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), rasagiline (Azilect), phenelzine (Nardil), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate).
You may have thoughts about suicide when you first start takinganantidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.
Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.
Olanzapine can cause high blood sugar (hyperglycemia). If you are diabetic, check your blood sugar levels on a regular basis while you are taking Symbyax.
SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Symbyax, do not stop taking the medication without first talking to your doctor.
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Before taking Symbyax
Symbyax is not for use in psychotic conditions related to dementia. Olanzapine may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions. Do not use Symbyax if you are using any of the following drugs:
pimozide (Orap);
thioridazine (Mellaril); oran MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam).
Serious and sometimes fatal reactions can occur when these medicines are taken with Symbyax. You must wait at least 14 days after stopping an MAO inhibitor before you can take Symbyax.
You must wait 5 weeks after stopping Symbyax before you can take thioridazine (Mellaril) or an MAO inhibitor.
If you have any of these other conditions, you may need a Symbyax dose adjustment or special tests:
liver disease;
heart disease, high or low blood pressure, or a history of heart attack or stroke;
diabetes;
high cholesterol or triglycerides;
seizures or epilepsy;
narrow-angle glaucoma;
paralytic ileus (a stomach disorder);
breast cancer;
enlarged prostate; ora history of drug abuse or suicidal thoughts.
You may have thoughts about suicide when you first start taking anantidepressant such as Symbyax, especially if you are younger than 24 years old.
Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.
Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.
FDA pregnancy category C. An SSRI antidepressant may cause serious lung problems in a newborn if you take the medication during pregnancy. However, you may have a relapse of depression if you stop takingyourantidepressant during pregnancy. If you become pregnant while taking Symbyax, do not stop taking the medication without first talking to your doctor.
Fluoxetine and olanzapine can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are taking Symbyax. Do not give Symbyax to anyone younger than 18 years old without the advice of a doctor.
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How should I take Symbyax?
Take Symbyax exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended.
Follow the directions on your prescription label.
Symbyax can be taken with or without food. Try to take the medicine at the same time each day.
It may take up to 4 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment.
Olanzapine can cause high blood sugar (hyperglycemia). If you are diabetic, check your blood sugar levels on a regular basis while you are taking Symbyax.
Store Symbyax at room temperature away from moisture and heat.
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What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
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What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include nausea, vomiting, tremor, problems with speech or vision, seizure (convulsions), and coma.
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What should I avoid while taking Symbyax?
Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking Symbyax. Drinking alcohol can increase certain side effects of fluoxetine and olanzapine.
Symbyax may impair your thinking or reactions. Be careful if you drive ordoanything that requires you to be alert.
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Symbyax side effects
Get emergency medical help if you have any of these signs of an allergic reaction to Symbyax: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.
Call your doctor at once if you have a serious side effect such as:
sudden and severe headache, chest pain, numbness, and problems with vision, speech, or balance;increased thirst, frequent urination, excessive hunger, or
weakness;agitation, hallucinations, fever, fast heart rate, overactive reflexes, vomiting, diarrhea, loss of coordination;very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;jerky muscle movements you cannot control;seizure (convulsions);
feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;flu symptoms, easy bruising, sores in your mouth and throat; ornausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Less serious Symbyax side effects may include:
trouble swallowing, runny nose, sore throat;
weight gain, swelling in your hands of feet;
drowsiness, trouble concentrating, sleep problems (insomnia);
dry mouth, mild diarrhea, increased appetite;
breast swelling or discharge (in women or men);
missed menstrual periods; ordecreased sex drive, impotence, or difficulty having an orgasm.
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.
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What other drugs will affect Symbyax?
Ask your doctor before taking any medicine for pain, arthritis, fever, or swelling.
This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin, piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others.
Taking any of these drugs with Symbyax may cause you to bruise or bleed easily.
Before using Symbyax, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety). They can add to sleepiness caused by Symbyax.
Tell your doctor about all other medicines you use, especially:vinblastine (Velban);
heart rhythm or blood pressure medication;tryptophan (sometimes called L-tryptophan);lithium, clozapine (Clozaril, Fazaclo), haloperidol (Haldol);
phenytoin (Dilantin), carbamazepine (Carbatrol, Tegretol);a blood thinner such as warfarin (Coumadin);another form of fluoxetine or olanzapine such as Prozac,
Prozac Weekly, Sarafem, or Zyprexa;theophylline (Theo-Dur, TheoBid, Uniphyl, Slo-Bid, Elixophyllin, and others);medicine to treat Parkinson's disease, suchasbromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex),
ropinorole (Requip), or cabergoline (Cabaser);almotriptan (Axert), frovatriptan (Frova), sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt), orzolmitriptan (Zomig); orany other antidepressants.
This list is not complete and other drugs may interact with Symbyax. Tell your doctor about all medications you use.
This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
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Where can I get more information?
Your pharmacist can provide more information about Symbyax. Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect.
Druginformationcontained herein may be time sensitive. 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.
The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.
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