【药品名称】 通用名：富马酸喹硫平片 商品名：思瑞康/SEROQUEL 英文名：Quetiapine fumarate Tablet 其结构式为： 【性状】 25毫克片：圆形，6毫米，粉红色，双凸，包衣片剂。 100毫克片：圆形，8.5毫米，黄色，双凸，包衣片剂。 200毫克片：圆形，11毫米，白色，双凸，包衣片剂。 【药理毒理】 药效学特性 喹硫平是一种非经典抗精神病药物，对多种神经递质受体有相互作用。在脑中，喹硫平对五羟色胺（5HT2）受体具有高度亲和力，且大于对脑中多巴胺D1和多巴胺D2受体的亲和力。喹硫平对组织胺受体和肾上腺素能α1受体同样有高亲和力，对肾上腺素能α1受体亲和力低，但对胆碱能毒受体或苯二氮卓受体基本没有亲和力。喹硫平对抗精神病药物活性测定如条件回避反射呈阳性结果。 喹硫平片不产生持久的催乳素升高现象。在一项多剂量临床试验中发现，不同剂量喹硫平组所出现的催乳素水平变化没有差异，与安慰剂组之间也无差异。 临床试验显示，喹硫平片对治疗精神分裂症的阳性和阴性症状均有效。一项与氯丙嗪，两项与氟哌啶醇对照的试验显示，喹硫平片的短期疗效与对照药物相当。 毒理学 急性毒性研究 喹硫平的急性毒性很低。给小鼠和大鼠口服（500毫克/公斤）或腹腔注射（100毫克/公斤）后出现典型的抗精神病药物的效应。 重复给药毒性研究 给大鼠、狗和猴子重复使用喹硫平，可见预期的抗精神病药物样中枢神经系统作用（如低剂量时镇静、高剂量时震颤抽搐或虚弱）。 与肝酶诱导相一致的对肝脏的可逆性形态学和功能影响见之于小鼠、大鼠和猴子。 甲状腺细胞增生和相应的血浆甲状腺激素水平的变化可见之于大鼠和猴子。 在狗身上曾发生一过性心率增加，但不伴随对血压的影响。 在剂量达到225毫克/公斤/日给予猴子或啮齿类动物均未发现白内障。在人类的临床研究监测中未发现有与药物有关的角膜浑浊。 所有的毒性研究中均未发现有中性粒细胞下降或粒细胞缺乏症。 生殖毒性研究 喹硫平无致畸作用。 致突变研究 对喹硫平的遗传毒理研究显示，喹硫平无致突变及致断裂作用。 【药代动力学】 喹硫平口服后吸收良好，代谢完全。人类血浆中主要的代谢产物不具有明显药理学活性。进食对喹硫平的生物利用度无明显影响。喹硫平的消除半衰期大约为7小时。83%的喹硫平与血浆蛋白结合。 临床试验证实，每日两次给药时喹硫平是有效的。正电子发射断层摄影术（PET）研究资料进一步证实，该药对5HT2和D2受体的占据作用在给药后可持续12小时。 喹硫平的药代动力学是线性的，男女无差别。 老年人喹硫平的平均清除率较18－65岁成年人低30－50%。 严重肾损害（肌酐清除率低于30ml/min/1.73m2）和肝损害（稳定性酒精性肝硬化）的患者，喹硫平的平均血浆清除率可下降约25%，但个体清除率值都在正常人群范围之内。 喹硫平代谢较完全，服用放射性标记的喹硫平后尿或粪便中原形化合物仅占的药物及相关物质的 5%以下。大约73%的放射活性代谢物从尿中排出，21%从粪便中排出。 离体研究证实喹硫平的主要代谢酶为细胞色素P450酶系统的CYP3A4。 喹硫平及其几种代谢产物是细胞色素P450酶1A2，2C9，2C19，2D6和3A4的弱抑制剂，但只在高于300－450毫克/日的人类有效剂量的10－50倍的浓度时才出现。 【适应症】喹硫平片用于治疗精神分裂症。 【用法与用量】喹硫平片应每日两次给药，饭前饭后均可。 成人 前4天治疗期的日总剂量为50毫克（第一日），100毫克（第二日），200毫克（第三日）和300毫克（第四日）。从第四日以后，将剂量逐渐增加到400－600毫克/日。可根据病人的临床反应和耐受性将剂量在150－750 毫克/日之间调整。 老年 老年人的起始剂量应为25毫克/日。每日增加剂量，幅度为25－50毫克，直到有效剂量。有效剂量可能较一般年轻病人低。 儿童和青少年 喹硫平片用于儿童和青少年的安全性和有效性尚未进行评价。 肾脏和肝脏损害 口服喹硫平后的清除率在肾脏和肝脏损伤的病人中下降约25％。喹硫平在肝脏中代谢广泛，因此应慎用于肝脏损害的患者。 有肾脏或肝脏损害的病人，喹硫平片的开始剂量应为25毫克/日。随后每日增加剂量，幅度为25－50毫克，直到有效剂量或遵医嘱。 【不良反应】喹硫平短期对照试验中所报告的最常见和最显著的不良事件为：困倦（17.5%），头晕（10%），便秘（9%），体位性低血压（7%），口干（7%），以及肝酶异常（6%）。 与其它具有α1肾上腺素能阻断作用的抗精神病药物一样，喹硫平片可能导致直立性低血压（伴有头晕），心悸，某些病人会有晕厥；这些事件易发生于开始的剂量增加期。 偶有报道服用喹硫平片的病人出现癫痫，但其发生率并不高于安慰剂组。 与其它抗精神病药物一样，用喹硫平片治疗的病人罕见有神经阻滞剂恶性综合征。 与其它抗精神病药物一样，服用喹硫平片会伴有白细胞计数改变，在临床对照试验中所报告的发生率为1.6%。偶尔有嗜酸性粒细胞增加的报道。 在服用喹硫平片的某些病人曾观察到出现无症状的血清转氨酶（ALT，AST）或 ψ－GT水平增高。这种增高通常在继续喹硫平片治疗过程中恢复。在喹硫平片治疗过程中曾观察到有非空腹状态下血清甘油三酯和总胆固醇水平轻微升高现象。 喹硫平片治疗可伴有轻微的与剂量有关的甲状腺激素水平下降，尤其是总T4和游离T4。几乎所有的病人在停用喹硫平后其对总T4和游离T4的影响可以恢复. 【禁忌】喹硫平片禁用于对该产品的任何成份过敏的病人。 【注意事项】 心血管疾病 在临床试验中，使用喹硫平不伴发持久性QTC 间期的延长。但与其它抗精神病药物一样，如果将喹硫平与其它已知会延长QTC 间期的药物合用时应当谨慎，尤其是用于老年人。 癫痫 与其它抗精神病药物一样，当用于治疗有癫痫病史的患者时应予以注意。 对开车和操纵机器的影响 由于喹硫平片可能会导致困倦。因此对操纵危险机器包括开车的病人应予提醒。 【孕妇及哺乳期妇女用药】喹硫平片用于人类妊娠时的疗效和安全性尚未肯定。喹硫平在人类乳汁中的排泄情况尚不清楚。哺乳妇女若服用喹硫平应劝其在服药期间中断哺乳。 【药物相互作用】喹硫平片与锂合用不会影响锂的药代动力学,不会诱导与安替比林代谢有关的肝脏酶系统。喹硫平片和苯妥英合用可增加喹硫平的清除率。如果将喹硫平与苯妥英或其它肝酶诱导剂（如卡马西平、巴比妥类、利福平）合用，为保持抗精神病症状的效果，应增加喹硫平片的剂量。如果停用苯妥英并换用一种非诱导剂（如丙戊酸钠）则喹硫平片的剂量需要减少。 合用抗精神病药物利培酮或氟哌啶醇不会显著改变喹硫平的药代动力学。但喹硫平片与硫利达嗪合用时会增加喹硫平的清除率。 与抗抑郁药丙咪嗪或氟西汀合用不会显著改变喹硫平的药代动力学。 在细胞色素酶P450中，介导代谢的主要酶类为CYP3A4。与西咪替丁（CIMETIDINE）或氟西汀（两种药物都是已知的P450酶抑制剂）合用不会改变喹硫平的药代动力学。但如果喹硫平片与CYP3A4的强抑制剂[如全身应用的酮康唑（KETOCONAZOLE）或红霉素]合用需谨慎。 【药物过量】一般情况下，所报告的症状和体征是该药的已知药理学作用的增强，即困倦和镇静，心悸和低血压。有人曾服用超过10g喹硫平片未致死，而且病人完全恢复无后遗症。 喹硫平无特异性解毒剂。遇到严重中毒的病人，应考虑多种药物介入的可能性，并建议采取积极的监护措施，包括开辟良好的气道，保证适当的氧气供应和呼吸，并且监测和维持心血管系统功能。 【包装】20片/盒。铝塑泡包装。 【贮藏】30℃ 以下存放。  【有效期】3年。 【生产企业】：AstraZeneca UK Limited Seroquel Generic name: Quetiapine fumarate -------------------------------------------------------------------------------- Why is Seroquel prescribed? Seroquel is prescribed for the treatment of schizophrenia, a mental disorder marked by delusions (false beliefs), hallucinations, disrupted thinking, and loss of contact with reality. It is also used for the treatment of manic and depressive episodes associated with bipolar disorder. Seroquel belongs to one of the newer classes of antipsychotic medications. Researchers believe that it works by diminishing the action of dopamine and serotonin, two of the brain's chief chemical messengers. -------------------------------------------------------------------------------- Most important fact about Seroquel Seroquel may cause tardive dyskinesia, a condition characterized by uncontrollable muscle spasms and twitches in the face and body. This problem can be permanent, and appears to be most common among older adults, especially women. Seroquel is not approved for use in elderly patients with dementia (including Alzheimer's disease) due to the increased risk of sudden death, heart failure, and pneumonia. Antidepressants can increase the risk of suicidal thinking and behavior in children and teenagers. Both adult and pediatric patients taking antidepressants should be watched closely for changes in moods or actions, especially when they first start therapy or when their dose is increased or decreased. Patients and their families should contact the doctor immediately if new symptoms develop or seem to get worse. Signs to watch for include anxiety, hostility, insomnia, restlessness, impulsive or dangerous behavior, and thoughts about suicide or dying. Seroquel is not approved for use in pediatric patients. -------------------------------------------------------------------------------- How should you take Seroquel? Your doctor will increase your dose gradually until the drug takes effect. If you stop Seroquel for more than 1 week, you'll need to build up to your ideal dosage once again. If you miss a dose. Take it as soon as you remember. If it is almost time for the next dose, skip the one you missed and go back to your regular schedule. Do not take 2 doses at once. Storage instructions. Store at room temperature. -------------------------------------------------------------------------------- What side effects may occur? Side effects cannot be anticipated. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Seroquel. Side effects may include: Abdominal pain, constipation, diminished movement, dizziness, drowsiness, dry mouth, excessive muscle tone, headache, indigestion, low blood pressure (especially upon standing), nasal inflammation, neck rigidity, rapid or irregular heartbeat, rash, sleepiness, tremor, uncontrollable movements, weakness -------------------------------------------------------------------------------- Why should Seroquel not be prescribed? If Seroquel gives you an allergic reaction, you will not be able to use this drug. -------------------------------------------------------------------------------- Special warnings about Seroquel Call your doctor immediately if you develop muscle stiffness, confusion, irregular or rapid heartbeat, excessive sweating, and high fever. These are signs of Neuroleptic Malignant Syndrome (NMS), a serious—and potentially fatal—reaction to the drug. Be especially wary if you have a history of heart attack, heart disease, heart failure, circulation problems, or irregular heartbeat. Particularly during the first few days of therapy, Seroquel can cause low blood pressure, with accompanying dizziness, fainting, and rapid heartbeat. To minimize these effects, your doctor will increase your dose gradually. If you are prone to low blood pressure, take blood pressure medication, or become dehydrated, use Seroquel with caution. Seroquel also tends to cause drowsiness, especially at the start of therapy, and can impair your judgment, thinking, and motor skills. Until you are certain of the drug's effect, use caution when operating machinery or driving a car. Certain antipsychotic drugs, including Seroquel, are associated with an increased risk of developing high blood sugar, which on rare occasions has led to coma or death. See your doctor right away if you develop signs of high blood sugar, including dry mouth, unusual thirst, increased urination, and tiredness. If you have diabetes or have a high risk of developing it, see your doctor regularly for blood sugar testing. People at high risk of suicide attempts should be prescribed the lowest dose possible to reduce the risk of intentional overdose. Animal studies suggest that Seroquel may increase the risk of breast cancer, although human studies have not confirmed such a risk. If you have a history of breast cancer, see your doctor regularly for checkups. If you are having problems with your vision, tell your doctor. There is a chance that Seroquel may cause cataracts, and you may be asked to see an eye doctor when you start Seroquel therapy, and every 6 months thereafter. Seroquel poses a very slight risk of seizures, especially if you are over 65, have epilepsy, or have a condition that increases the risk of seizures. The drug can also suppress an underactive thyroid, and generally causes a minor increase in cholesterol levels. There is also a remote chance that it will trigger a prolonged and painful erection. Other antipsychotic medications have been known to interfere with the body's temperature-regulating mechanism, causing patients to overheat. Although this problem has not occurred with Seroquel, caution is still advisable. Avoid exposure to extreme heat, strenuous exercise, and dehydration. Seroquel is prescribed for the short-term treatment of rapid-onset bipolar mania; it is not approved for preventing future episodes. The effectiveness of the drug for treating mania for more than 3 weeks has not been studied. The safety and effectiveness of Seroquel have not been studied in children. -------------------------------------------------------------------------------- Possible food and drug interactions when taking Seroquel Seroquel increases the effects of alcohol. Avoid alcoholic beverages while on Seroquel therapy. If Seroquel is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Seroquel with the following: Barbiturates such as phenobarbital Carbamazepine Cimetidine Erythromycin Fluconazole Itraconazole Ketoconazole Levodopa Lorazepam Phenytoin Rifampin Steroid medications such as hydrocortisone and prednisone Thioridazine -------------------------------------------------------------------------------- Special information if you are pregnant or breastfeeding The possibility of harm to a developing baby has not been ruled out. You should take Seroquel during pregnancy only if the benefits outweigh this potential risk. Notify your doctor as soon as you become pregnant or decide to become pregnant. It is not known whether Seroquel appears in breast milk, and breastfeeding is not recommended. -------------------------------------------------------------------------------- Recommended dosage for Seroquel SCHIZOPHRENIA Adults The usual dosage range is 300 to 400 milligrams a day, divided into two or three smaller doses. Doses as low as 150 milligrams a day sometimes prove effective, and the dose rarely exceeds 750 milligrams per day. Doses above 800 milligrams per day have not been tested for safety. The dose is gradually increased over 4 days until the most effective dose is reached, using the following schedule: Day 1: Take 25 milligrams twice a day. Days 2, 3, and 4: The doctor will increase each daily dose by 25 to 50 milligrams, taken either two or three times a day. Day 5 and up: If needed, the doctor may increase each dose by 25 to 50 milligrams every 2 or more days. BIPOLAR MANIA (SHORT-TERM TREATMENT OF ACUTE EPISODES) Adults The usual dosage range is 400 to 800 milligrams a day. Doses above 800 milligrams a day have not been tested for safety. The dosage will be gradually increased over 4 to 6 days until the most effective dose is reached, using the following schedule: Day 1: Take 50 milligrams twice a day. Day 2: The doctor will increase the dose to 100 milligrams twice a day. Day 3: The doctor will increase the dose to 150 milligrams twice a day. Day 4: The doctor will increase the dose to 200 milligrams twice a day. Days 5 and 6: If needed, the doctor may increase each dose by no more than 200-milligram increments to a total daily dose of 800 milligrams. BIPOLAR DEPRESSION Adults The usual dose is 300 milligrams once a day at bedtime. The dosage will be gradually increased over 4 days using the following schedule: Day 1: Take 50 milligrams at bedtime. Day 2: The doctor will increase the dose to 100 milligrams at bedtime. Day 3: The doctor will increase the dose to 200 milligrams at bedtime. Day 4: The doctor will increase the dose to 300 milligrams at bedtime. DOSAGE ADJUSTMENT If you have liver problems, you may be started at 25 milligrams a day. The doctor will increase the dose as needed in increments of 25 to 50 milligrams a day based on your body's response. The dosage may also need to be lowered if you are weak, elderly, or prone to low blood pressure reactions. You may also need your dose adjusted if you're taking certain drugs, including Dilantin, Tegretol, and phenobarbital. -------------------------------------------------------------------------------- Overdosage Any medication taken in excess can have serious consequences. If you suspect an overdose, seek medical help immediately. Symptoms of Seroquel overdose may include: Dizziness, drowsiness, fainting, rapid heartbeat 躁郁症患者在服用SEROQUEL (Quetiapine)后病人病情有所缓解   日前宣布临床数据表明，患有与使人虚弱的精神疾病??躁郁症有关的狂躁症状的患者在用quetiapine（喹硫平）治疗后，与服用安慰剂（一粒糖丸）的患者相比，达到正常情绪水平和狂躁症状缓解的可能性要增加很多。 在美国精神病学协会（APA）第157次大会上提出的这项研究的结果显示，在用quetiapine治疗三周后，超过三分之一的患者病情有所缓解或达到正常的情绪水平。此外，治疗12周的较长时间的数据表明，服用quetiapine的患者中多数(61%)出现了这样的结果，症状持续改善。 躁郁症是一种严重的精神疾病，它影响到成年人口的大约3％至4%，是世界第六大致残原因。躁郁症患者中有超过半数的人在患病的某个时候停止服药，使他们有很高的复发危险，自杀的危险也有所增加。因此，一种药物的总药效和可忍受性对于帮助患者按规定服药是至关重要的。 在APA上提出的其它一些数据也支持了这些结果。这些数据显示，用quetiapine加情绪稳定药物治疗的患者们的躁狂症状的缓解率（38.4%）比单纯使用情绪稳定药物治疗（25.9%）的高得多。患者对Quetiapine的忍受情况普遍很好。 Quetiapine在欧洲和美国已经获得了用于治疗与躁郁症有关的躁狂症状的许可。在另外23个国家和地区还获得了用于治疗躁郁症的许可。自1997年以来，Quetiapine已被许可用于治疗精神分裂症，现在在81个国家和地区内使用。