近日，美国食品和药物管理局（FDA）已批准INVEGA（paliperidone）缓释片每日一次，一个新的，非典型抗精神病药物，长期维持治疗精神分裂症。
批准日期：2015年5月25日 公司：强生(JNJ)
NVEGA（帕潘立酮 paliperidone）缓释片,供口服使用
美国最初批准：2006年
警告：患有与痴呆症有关的精神疾病的老年患者的死亡率增加，请参阅完整的拳击警告的完整预定信息。
用抗精神病药治疗的老年痴呆相关精神病患者死亡风险增加。 INVEGA®未被批准用于痴呆相关精神病患者。
最近的重大变化
警告和注意事项：07/2018
警告和注意事项，自杀已被删除07/2018
警告和注意事项，监控：实验室测试已于07/2018删除
作用机制
帕潘立酮是利培酮的主要活性代谢产物。 帕潘立酮在精神分裂症中的作用机制尚不清楚。 然而，药物在精神分裂症中的治疗效果可以通过中枢多巴胺2型（D2）和血清素2型（5HT2A）受体拮抗作用来介导。
适应症和用法
INVEGA®是一种非典型抗精神病药物
治疗精神分裂症。
成人：在三个为期6周的试验和一个维持试验中确定了疗效。
青少年（12-17岁）：在一项为期6周的试验中确定了疗效。
将分裂情感障碍作为单一疗法和作为情绪稳定剂和/或抗抑郁药的辅助治疗。
在成人患者的两个为期6周的试验中确立了疗效。
剂量和给药
                   初始剂量   推荐剂量    最大剂量
精神分裂症-成年人  6毫克/天  3-12毫克/天  12毫克/天
        重量<51kg  3毫克/天  3-6毫克/天   6毫克/天
精神分裂症，青少年
        重量≥51kg 3毫克/天  3-12毫克/天  12毫克/天
分裂情感障碍-成人  6毫克/天  3-12毫克/天  12毫克/天
片剂应整个吞服，不应咀嚼，分割或压碎。
剂量形式和强度
片剂：1.5mg，3mg，6mg和9mg
禁忌症
已知对帕利哌酮，利培酮或INVEGA®中任何赋形剂的超敏反应。
警告和注意事项
脑血管不良反应：在使用非典型抗精神病药治疗的痴呆相关精神病患者中，脑血管不良反应（例如中风，短暂性脑缺血发作，包括死亡）的发生率增加。
神经阻滞性恶性综合症：立即停药并密切监测。
QT延长：QT间期增加，避免使用同时增加QT间期的药物和有QT间期延长的危险因素的患者。
迟发性运动障碍：如果临床适当，停用药物。
代谢变化：非典型抗精神病药物与可能增加心血管/脑血管风险的代谢变化有关。这些代谢变化包括高血糖，血脂异常和体重增加。
高血糖和糖尿病：监测患者的高血糖症状，包括烦渴，多尿，多食和虚弱。定期监测糖尿病患者或有糖尿病风险的患者。
血脂异常：在用非典型抗精神病药物治疗的患者中观察到不希望的改变。
体重增加：据报道体重增加显着。监测体重增加。
高催乳素血症：在长期给药期间出现催乳素升高并持续存在。
胃肠道狭窄：阻塞性症状可能导致胃肠道疾病患者。
直立性低血压和晕厥：对已知心血管或脑血管疾病的患者和容易发生低血压的患者慎用。
白细胞减少症，中性粒细胞减少症和粒细胞缺乏症：已报道抗精神病药，包括INVEGA®。具有临床显着低白细胞计数（WBC）或药物诱导的白细胞减少/中性粒细胞减少症史的患者应在治疗的最初几个月内经常监测其全血细胞计数（CBC），并应考虑停用INVEGA®在没有其他致病因素的情况下，WBC临床显着下降的第一个迹象。
认知和运动损伤的可能性：操作机器时要小心。
癫痫发作：对有癫痫病史或癫痫发作阈值降低的病人慎用。
不良反应
常见的不良反应（发生率≥5％，至少是安慰剂的两倍）。
精神分裂症患者：锥体外系症状，心动过速和静坐不能。
患有精神分裂症的青少年：嗜睡，静坐不能，震颤，肌张力障碍，齿轮僵硬，焦虑，体重增加和心动过速。
患有分裂情感障碍的成人：锥体外系症状，嗜睡，消化不良，便秘，体重增加和鼻咽炎。
要报告疑似不良反应，请致电1-800-JANSSEN（1-800-526-7736）或FDA 1-800-FDA-1088或www.fda.gov/medwatch联系Janssen Pharmaceuticals，Inc
药物相互作用
中枢作用药物：由于中枢神经系统的影响，请谨慎使用。避免酒精。
可能导致直立性低血压的药物：与INVEGA®共同给药时可能会观察到累加效应。
强CYP3A4/P-糖蛋白（P-gp）诱导剂：当共同施用CYP3A4和P-gp（例如卡马西平）的强诱导剂时，可能需要增加INVEGA®的剂量。相反，在停止使用强诱导剂时，可能需要减少INVEGA®的剂量。
双丙戊酸钠的共同给药使帕潘立酮的Cmax和AUC增加约50％。根据临床评估，根据需要调整INVEGA®的剂量。
用于特定人群
肾功能损害：给药必须根据肾功能状态进行个体化。
老年人：与年轻人相同（根据肾功能状态调整剂量）。
怀孕：在妊娠晚期接触的新生儿可能会导致锥体外系和/或戒断症状。
儿科用途：治疗精神分裂症的安全性和有效性，不适用于12岁以下的患者。治疗分裂情感障碍的安全性和有效性未在18岁以下的患者中确立。
包装提供/存储和处理
INVEGA®（帕潘立酮）缓释片具有以下优势和包装。 所有片剂均为胶囊状。
1.5毫克片剂为橙棕色并印有“PAL 1.5”，可以30瓶装（NDC 50458-554-01）。
3mg片剂是白色的并且印有“PAL 3”，并且可以30瓶（NDC 50458-550-01）和100单位的医院单位剂量包（NDC 50458-550-10）获得。
6毫克片剂为米色并印有“PAL 6”，并且有30瓶（NDC 50458-551-01）和100单位的医院单位剂量包（NDC 50458-551-10）。
9毫克片剂为粉红色并印有“PAL 9”，有30瓶（NDC 50458-552-01）和100单位的医院单位剂量包（NDC 50458-552-10）。
存储和处理
储存温度最高可达25°C（77°F）; 允许偏移15 - 30°C（59 - 86°F）[见USP受控室温]。 防潮。
请将本品放在儿童不能接触的地方。
完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b8e5b26-b9e4-4704-921b-3c3c0d159916
INVEGA(paliperidone)Extended-Release Tablets
INVEGA® (paliperidone) extended-release tablets are indicated for the treatment of schizophrenia in adults and adolescents (12-17 years of age). The efficacy of INVEGA® in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (12-17 years of age), as well as one maintenance trial in adults.
INVEGA® (paliperidone) extended-release tablets are indicated for the treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressant therapy in adults. The efficacy of INVEGA® in schizoaffective disorder was established in two 6-week trials in adults.
Important Safety Information
INVEGA® (paliperidone) is used for the short-term treatment of schizoaffective disorder in adults and for the treatment of schizophrenia in adults and in adolescents (12-17 years of age).
INVEGA® is not approved for the treatment of dementia-related psychosis in elderly patients. Elderly patients who were given oral antipsychotics like INVEGA® in clinical studies for psychosis caused by dementia (memory problems) had a higher risk of death.
Do not receive INVEGA® if you are allergic to paliperidone, risperidone, or any of the ingredients in INVEGA®
Neuroleptic Malignant Syndrome (NMS) is a rare but serious side effect that could be fatal and has been reported with INVEGA® and similar medicines. Call your doctor right away if you develop symptoms such as a high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness. Treatment should be stopped if you are being treated for NMS.
Tardive Dyskinesia (TD) is a rare but serious and sometimes permanent side effect reported with INVEGA® and similar medicines. Call your doctor right away if you start to develop twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body. The risk of developing TD and the chance that it will become permanent is thought to increase with the length of therapy and the total dose received. This condition can also develop after a short period of treatment at low doses, but this is less common. There is no known treatment for TD, but it may go away partially or completely if the medicine is stopped.
One risk of INVEGA® is that it may change your heart rhythm. This effect is potentially serious. You should talk to your doctor about any current or past heart problems. Because these problems could mean you're having a heart rhythm abnormality, contact your doctor IMMEDIATELY if you feel faint or feel a change in the way that your heart beats (palpitations).
Atypical antipsychotic drugs have been associated with metabolic changes that can increase cardiovascular/cerebrovascular risks. These changes may include:
High blood sugar and diabetes have been reported with INVEGA® and similar medicines. If you already have diabetes or have risk factors such as being overweight or a family history of diabetes, blood sugar testing should be done at the beginning and during the treatment. The complications of diabetes can be serious and even life-threatening. Call your doctor if you develop signs of high blood sugar or diabetes, such as being thirsty all the time, having to urinate or "pass urine" more often than usual, or feeling weak or hungry.
Changes in cholesterol and triglycerides have been noted in patients taking atypical antipsychotics. Check with your doctor while on treatment.
Weight gain has been reported in patients taking atypical antipsychotics. Monitor weight gain while on treatment. For adolescent patients (12-17 years of age) weight gain should be assessed against that expected with normal growth.
People with narrowing or blockage of the gastrointestinal tract (esophagus, stomach, or small or large intestine) should talk to their healthcare professional before taking INVEGA®.
Some people may feel faint, dizzy, or may pass out when they stand up or sit up suddenly. Be careful not to get up too quickly. It may help if you get up slowly and sit on the edge of the bed or chair for a few minutes before you stand up. These symptoms may decrease or go away after your body becomes used to the medicine.
Patients (particularly the elderly) taking antipsychotics with certain health conditions or those on long-term therapy should be eva luated by their healthcare provider for the potential risk of falls.
INVEGA® and similar medicines have been associated with decreases in the counts of white cells in circulating blood. If you have a history of low white blood cell counts or have unexplained fever or infection, then please contact your doctor right away.
INVEGA® and similar medicines can raise the blood levels of a hormone called prolactin, and blood levels of prolactin remain high with continued use. This may result in some side effects, including missed menstrual periods, leakage of milk from the breasts, development of breasts in men, or problems with erection.
If you have a prolonged or painful erection lasting more than 4 hours, seek immediate medical help to avoid long-term injury.
INVEGA® should be used cautiously in people with a seizure disorder, who have had seizures in the past, or who have conditions that increase their risk for seizures.
Call your doctor right away if you start thinking about suicide or wanting to hurt yourself.
INVEGA® can make some people feel dizzy, sleepy, or less alert. Until you know how you are going to respond to INVEGA®, be careful driving a car, operating machines, or doing things that require you to be alert.
This medicine may make you more sensitive to heat. You may have trouble cooling off or be more likely to become dehydrated. Be careful when you exercise or spend time doing things that make you warm.
INVEGA® should be swallowed whole. Tablets should not be chewed, divided, or crushed. Do not be worried if you see something that looks like a tablet in your stool. This is what is left of the tablet after all the medicine has been released.
Do not drink alcohol while you are taking INVEGA®.
The most common side effects that occurred with INVEGA® in the treatment of schizophrenia in adults were: abnormal muscle movements (including tremor [shaking]), shuffling, uncontrolled involuntary movements, and abnormal movements of the eyes); feeling of inner restlessness or needing to be constantly moving; and fast heartbeat. The most common side effects that occurred with INVEGA® in the treatment of schizophrenia in adolescents were: drowsiness, abnormal muscle movement (including a feeling of inner restlessness or needing to be constantly moving, tremor [shaking], involuntary muscle contractions, stiff muscles making your movements jerky); feeling of inner restlessness or needing to be constantly moving; fast heartbeat, and anxiety (nervousness). The most common side effects that occurred with INVEGA® in the treatment of schizoaffective disorder in adults were: abnormal muscle movements (including tremor [shaking]), shuffling, uncontrolled involuntary movements, and abnormal movements of the eyes), sleepiness, heartburn, constipation, weight increase, and sore throat.