每月注射一次的抗精神病新型缓释注射用悬浮液已获FDA批准上市
近日。美国食品药品管理局(FDA)已批准Invega Sustenna(棕榈酸帕潘立酮)缓释混悬剂用于成人精神分裂症的紧急救治和维持治疗。Invega Sustenna是一种可注射的长效非典型抗精神病药，每月一次用药。
批准日期：2009年7月31日  公司：Janssen Pharmaceuticals，Inc
NVEGA SUSTENNA（帕潘立酮棕榈酸酯[paliperidone palmitate]）缓释注射用悬浮液，用于肌肉注射
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。 INVEGASUSTENNA®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：12/2017
作用机制
帕潘立酮棕榈酸酯被水解为帕潘立酮[见临床药理学]。 帕潘立酮是利培酮的主要活性代谢产物。 帕潘立酮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
INVEGASUSTENNA®是一种非典型的抗精神病药
治疗成人精神分裂症。
治疗成人情感分裂症作为单一疗法和作为情绪稳定剂或抗抑郁药的辅助物。
剂量和给药
仅用于肌肉注射。
每次注射必须由医疗保健专业人员进行。
对于三角肌注射，对于体重小于90 kg的患者使用1英寸23G针头，对于体重90 kg或以上的患者使用1½英寸22G针头。对于臀部注射，无论患者体重如何，均使用1½英寸22G针头。
   迹象      启动剂量     每月维护剂量     每月最大剂量
             （三角肌)    （三角肌或臀肌）
             第1天  第8天
精神分裂症   234毫克 156毫克  39-234毫克        234毫克
分裂情感障碍 234毫克 156毫克  78-234毫克        234毫克
首次注射后5周给药。用于治疗精神分裂症的推荐维持剂量为117mg。一些患者可以在额外的可用强度（39mg，78mg，156mg和234mg）内受益于更低或更高的维持剂量。使用可用的强度基于耐受性和/或功效调整剂量。在长期分裂情感障碍研究中未研究39mg强度。
对于初次口服帕潘立酮或口服或注射利培酮的患者，在开始使用INVEGASUSTENNA®治疗前，口服帕潘立酮或口服利培酮可耐受。
错过的剂量：要管理错过的第二次开始剂量或错过的每月维持剂量，请参阅完整的处方信息。
中度至重度肾功能损害（肌酐清除率<50mL/min）：不建议使用INVEGASUSTENNA®。
轻度肾功能损害（肌酐清除率≥50mL/min至<80mL/min）：治疗第1天给药156mg，一周后给药117mg，均在三角肌中给药。随后在三角肌或臀肌中每月注射78毫克。
剂量形式和强度
缓释可注射悬浮液：39mg，78mg，117mg，156mg或234mg
禁忌症
对INVEGASUSTENNA®中的帕潘立酮，利培酮或任何赋形剂都有超敏感性。
警告和注意事项
老年痴呆相关精神病患者的脑血管不良反应，包括中风：脑血管不良反应发生率增加（例如中风，短暂性脑缺血发作）。
神经阻滞性恶性综合症：立即停药并密切监测。
QT延长：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：监测高血糖/糖尿病，血脂异常和体重增加。
直立性低血压和晕厥：监测心率和血压，并警告患有已知心血管或脑血管疾病的患者，以及脱水或晕厥的风险。
白细胞减少症，中性粒细胞减少症和粒细胞缺乏症：对已有低白细胞计数（WBC）或白细胞减少或中性粒细胞减少症史的患者进行全血细胞计数（CBC）。如果在没有其他致病因素的情况下WBC临床显着下降，请考虑停用INVEGASUSTENNA®。
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。
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
最常见的不良反应（发生率≥5％，发生率至少是安慰剂的两倍）是注射部位反应，嗜睡/镇静，头晕，静坐不能和锥体外系障碍。
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
可能导致直立性低血压的药物：与INVEGASUSTENNA®共同给药时可能会产生累加效应。
强CYP3A4 / P-糖蛋白（P-gp）诱导剂：在INVEGASUSTENNA®的给药间隔期间避免使用强诱导剂CYP3A4和/或P-gp（例如卡马西平，利福平，圣约翰草）。如果需要使用强诱导剂，请考虑使用帕潘立酮缓释片治疗患者。
用于特定人群
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。
包装提供/存储和处理
INVEGASUSTENNA®有白色至灰白色无菌水性缓释释放悬浮液，可用于肌肉注射，剂量强度为39 mg，78 mg，117 mg，156 mg和234 mg帕潘立酮棕榈酸酯。 该套件包含一个预装注射器和2个安全针（1½英寸22号安全针和1英寸23号安全针）。
39mg帕潘立酮棕榈酸酯试剂盒（NDC 50458-560-01）
78mg帕潘立酮棕榈酸酯试剂盒（NDC 50458-561-01）
117mg帕潘立酮棕榈酸酯试剂盒（NDC 50458-562-01）
156mg帕潘立酮棕榈酸酯试剂盒（NDC 50458-563-01）
234mg帕潘立酮棕榈酸酯试剂盒（NDC 50458-564-01）
存储和处理
在室温下储存（25°C，77°F）; 允许在15°C至30°C（59°F至86°F）之间进行短距离游览。 不要与任何其他产品或稀释剂混合。
完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554
IMPORTANT SAFETY INFORMATION FOR INVEGA® SUSTENNA® (paliperidone palmitate)
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS.
•Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
•INVEGA® SUSTENNA® is not approved for the treatment of patients with dementia-related psychosis.
•See full Prescribing Information for Warnings and Precautions (5.1).
Contraindications: Paliperidone is contraindicated in patients with a known hypersensitivity to either paliperidone, risperidone, or to any components of the formulation.
Cerebrovascular Adverse Events (CAEs): Cerebrovascular Adverse Reactions (e.g., stroke, transient ischemic attacks), including fatalities, were reported in placebo-controlled trials in elderly patients with dementia-related psychosis taking oral risperidone, aripiprazole, and olanzapine. The incidence of Cerebrovascular Adverse Reactions was significantly higher than with placebo. INVEGA® SUSTENNA® is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with the use of antipsychotic medications, including paliperidone. Clinical manifestations include muscle rigidity, fever, altered mental status, and evidence of autonomic instability (see full Prescribing Information). Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and close medical monitoring, and treatment of any concomitant serious medical problems.
QT Prolongation: Paliperidone causes a modest increase in the corrected QT (QTc) interval. Avoid the use of drugs that also increase QTc interval and in patients with risk factors for prolonged QTc interval. Paliperidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Certain circumstances may increase the risk of the occurrence of torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.
Tardive Dyskinesia (TD): TD is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic medications. The risk of developing TD and the likelihood that dyskinetic movements will become irreversible are believed to increase with duration of treatment and total cumulative dose, but can develop after relatively brief treatment at low doses. Elderly female patients appeared to be at increased risk for TD, although it is impossible to predict which patients will develop the syndrome.
Prescribing should be consistent with the need to minimize the risk of TD (see full Prescribing Information). Discontinue drug if clinically appropriate. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death have been reported in patients treated with all atypical antipsychotics (APS). Patients starting treatment with APS who have or are at risk for diabetes mellitus should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia during treatment should also undergo fasting blood glucose testing. All patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia. Some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug.
Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Orthostatic Hypotension and Syncope: INVEGA® SUSTENNA® may induce orthostatic hypotension in some patients due to its alpha-blocking activity. INVEGA® SUSTENNA® should be used with caution in patients with known cardiovascular disease, cerebrovascular disease or conditions that would predispose patients to hypotension (e.g.dehydration, hypovolemia, treatment with antihypertensive medications). Monitoring should be considered in patients for whom this may be of concern.
Leukopenia, Neutropenia and Agranulocytosis have been reported with antipsychotics, including paliperidone. Patients with a history of clinically significant low white blood cell count (WBC) or drug-induced leukopenia/neutropenia should have frequent complete blood cell counts during the first few months of therapy. At the first sign of a clinically significant decline in WBC, and in the absence of other causative factors, discontinuation of INVEGA® SUSTENNA® should be considered. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue INVEGA® SUSTENNA® and have their WBC followed until recovery.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, INVEGA® SUSTENNA® elevates prolactin levels and the elevation persists during chronic administration. Paliperidone has a prolactin-elevating effect similar to risperidone, which is associated with higher levels of prolactin elevation than other antipsychotic agents.
Potential for Cognitive and Motor Impairment: Somnolence, sedation, and dizziness were reported as adverse reactions in subjects treated with INVEGA® SUSTENNA®. INVEGA® SUSTENNA® has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about performing activities that require mental alertness such as operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA® SUSTENNA® does not adversely affect them.
Seizures: INVEGA® SUSTENNA® should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold. Conditions that lower seizure threshold may be more preva lent in patients 65 years or older.
Administration: For intramuscular injection only. Care should be taken to avoid inadvertent injection into a blood vessel.
Drug Interactions: Strong CYP3A4 inducers: It may be necessary to increase the dose of INVEGA® SUSTENNA® when a CYP3A4 strong inducer (e.g. carbamazepine, rifampin, St. John’s wort) is added. It may be necessary to decrease the dose when a CYP3A4 strong inducer is discontinued.
Pregnancy/Nursing: Patients should be advised to notify their physician if they become pregnant/intend to become pregnant or intend to nurse during treatment with INVEGA® SUSTENNA®.
Commonly Observed Adverse Reactions for INVEGA® SUSTENNA®: The most common adverse reactions in clinical trials in patients with schizophrenia (≥5% and twice placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal disorder.  
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