VRAYLAR(cariprazine 中文药名：卡比米嗪胶囊)-获美国FDA批准新药治疗精神分裂和双相躁郁症 近日，美国FDA批准Forest Laboratories和Actavis Pharma的Vraylar（cariprazine，卡利拉嗪）上市，治疗成人精神分裂症（Schizophrenia）和狂躁型抑郁症（bipolar disorder）。 cariprazine是一种口服、每日一次的非典型抗精神病药物。在美国，该药已于2015年获准以品牌名Vraylar上市销售，目前已获批的适应症包括：（1）用于双相I型情感障碍（狂躁型抑郁症）成人患者狂躁或混合发作的紧急治疗，推荐的给药剂量范围为3-6mg/天；（2）用于精神分裂症成人患者的治疗，推荐的给药剂量范围为1.5-6.0mg/天。在欧盟，该药以品牌名Reagila上市销售。 批准日期：2015年9月17日；公司：Allergan和Gedeon Richter plc VRAYLAR(卡比米嗪 cariprazine)胶囊，供口服使用 美国初次批准：2015 作用机制 不知道卡比米嗪在精神分裂症和I型双相障碍的作用机制。但是，卡比米嗪的疗效可能被通过一个部分激动剂活性在中枢多巴胺D2和五羟色胺5-HT1A受体和在五羟色胺5-HT2A受体拮抗剂活性的组合介导。卡比米嗪形成两个主要代谢物，去甲基卡比米嗪(DCAR)和二去甲基卡比米嗪(DDCAR)，在体外有受体结合图形与母体药物受体结合图形相似。 适应症和用途 VRAYLAR是一种非典型抗精神病药物适用为： ⑴精神分裂症的治疗 ⑵ 双相Ⅰ型障碍相关躁狂或混合发作的急性治疗。 剂量和给药方法 ⑴给予VRAYLAR 1天1次有或无食物 ● 精神分裂症      开始剂量 1.5mg/day  推荐剂量  1.5mg至6mg/day ●双极性情感障碍   开始剂量 1.5mg/day  推荐剂量  3mg至6mg/day ⑵ 每天剂量6mg以上不提供显著获益但剂量相关不良反应的风险增加 剂型和规格 胶囊：1.5mg，3mg，4.5mg，和6mg 禁忌证 对VRAYLAR已知超敏性 警告和注意事项 ⑴心血管不良反应在老年患者有痴呆-相关精神病：心血管不良反应的发生率增加(如，卒中，短暂性脑缺血发作) ⑵ 抗精神病药物恶性症候群：处理用立即终止和密切监视 ⑶ 迟发性运动障碍：如适当终止 ⑷ 晚发生不良反应：因为VRAYLAR的长半衰期，开始VRAYLAR后监视不良反应和患者反应共几周和随每次剂量变化。 ⑸ 代谢变化：监视高血糖/糖尿病，血脂异常和体重增量 ⑹ 体位性低血压：监视心率和血压和警告有已知心血管或心血管病患者，和脱水或晕厥风险 不良反应 最常见不良反应(发生率 ≥ 5%和至少安慰剂率两倍)是： ⑴ 精神分裂症：锥体外系症状和静坐不能 ⑵双极性情感障碍：锥体外系症状，静坐不能，消化不良，呕吐，嗜睡，和躁动。 药物相互作用 ⑴ 强CYP3A4抑制剂：减低VRAYLAR剂量一半。 ⑵CYP3A4诱导剂：建议不与 VRAYLAR使用。 特殊人群中使用 妊娠：有第三个三个月暴露新生儿中可能致椎体外系和/或戒断症状。 精神分裂症新药Vraylar简介 Vraylar是口服的多巴胺D3/D2受体的部分激动剂，由匈牙利的Gedeon Richter制药公司研发。Gedeon Richter在2012年把Vraylar的美国和加拿大开发权转让给Forest Laboratories。多巴胺全名4-（2-氨基乙基）-1，2-苯二酚，是由大脑分泌的一种小分子胺类化合物。多巴胺是一种神经传导物质，能帮助细胞传送脉冲而影响情绪。 包装规格 VRAYLAR CAP 1.5MG-3MG 7  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0170-08 VRAYLAR CAP 1.5MG UD BP 2X10  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0115-20             VRAYLAR CAP 3MG UD BP 2X10  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0130-20 VRAYLAR CAP 1.5MG 30  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0115-30 VRAYLAR CAP 3MG 30  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0130-30 VRAYLAR CAP 4.5MG 30  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0145-30 VRAYLAR CAP 6MG 30  CARIPRAZINE HCL  ALLERGAN PHARMACEUTICAL  61874-0160-30  完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4b5f7c65-aa2d-452a-b3db-bc85c06ff12f ------------------------------------------------------------------ VRAYLAR™(cariprazine)capsules Important Safety Information 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. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. Contraindication VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and events suggestive of angioedema. Cerebrovascular Adverse Reactions, Including Stroke In clinical trials with antipsychotic drugs, elderly subjects with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities vs placebo. VRAYLAR 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 antipsychotics drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring. Tardive Dyskinesia (TD) Risk of developing TD (a syndrome of potentially irreversible, involuntary dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered. Late-Occurring Adverse Reactions Adverse events may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. Monitor for adverse reactions and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug. Metabolic Changes Atypical antipsychotics have caused metabolic changes, such as: •Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment. •Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment. •Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter. Leukopenia, Neutropenia, and Agranulocytosis Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Orthostatic Hypotension and Syncope Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases. Seizures Use VRAYLAR with caution in patients with history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle). Body Temperature Dysregulation Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics). Dysphagia Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration. Drug Interactions Strong CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended. Adverse Reactions In clinical trials, the most common adverse reactions (≥5% and at least twice the rate of placebo) are listed below. Dose-related increase in certain adverse reactions was observed, particularly above the maximum recommended dose of 6 mg/day. •Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5 – 3 mg/day and 4.5 – 6 mg/day vs placebo) were: extrapyramidal symptoms (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%) •Bipolar mania: The incidences within the recommended dose range (VRAYLAR 3 – 6 mg/day vs placebo) were: extrapyramidal symptoms (26% vs 12%), akathisia (20% vs 5%), dyspepsia (7% vs 4%), vomiting (10% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%)