近日，以色列的梯瓦制药在美国推出洛沙平 (Adasuve)，用于治疗与精神分裂症和双相情感障碍有关的焦虑。洛沙平最初由美国Alexza制药公司开发，并且是美国市场用于这种适应症的首款也是唯一一款吸入型抗精神病药物。
批准日期：公司：ALEXZA PHARMA INC
ADASUVE(洛沙平[loxapine])吸入粉末，用于口服吸入
美国首次批准：1975
警告：BRONCHOSPASM和老年患者死亡率增加痴呆相关精神病.
见完整处方信息完整盒装警告。
支气管痉挛
AdasuvE可能导致有可能导致支气管痉挛的支气管痉挛呼吸窘迫和呼吸骤停
AdasuVE只能通过一个受限制的程序风险评估和缓解策略（REMS）称为阿达苏弗雷姆斯.
•仅在注册的医疗机构中管理AdasuVE有立即进入现场的供应品和人员培训
急性支气管痉挛的治疗与紧急救治响应服务。设施必须有短效支气管扩张剂，包括喷雾器和吸入溶液，用于支气管痉挛的即时治疗
老年痴呆患者的死亡率增加精神病
老年痴呆相关精神病患者的治疗
抗精神病药物的死亡风险增加。
阿达苏未批准用于治疗痴呆患者
精神病
近期重大变化
装箱警告9/2016
警告和注意事项：9/2016
警告和注意事项：1/2017
作用机理
洛沙平治疗伴发躁动的作用机制
精神分裂症是未知的。然而，它的功效可以通过组合来介导。中枢多巴胺D2和5-羟色胺5-HT2A受体的拮抗作用的机制，loxapine在治疗躁郁症伴躁郁症中的作用尚不清楚。
适应症及用法
ADASUVE是一种典型的抗精神病药，用于急性治疗。
与成人精神分裂症或双极性I症相关的躁动。
2例急性躁动试验的疗效：
精神分裂症与双相I型障碍
使用限制：
AdasuVE必须只在注册的医疗机构管理。
剂量与给药
必须由医务人员管理
使用吸入剂口服吸入10毫克
在任何24小时内只注射一剂
在管理之前，筛查所有患者的肺部病史。
疾病，检查病人（包括胸部听诊）呼吸异常（如喘息）
参阅有关使用的重要指示的完整处方信息
无刺激性吸入器
管理后，监测患者的症状和体征。
支气管痉挛至少每15分钟至少1小时
剂型和强度
吸入粉末：单次吸入器10mg单位
禁忌症
哮喘、慢性阻塞性肺疾病的诊断或病史疾病（COPD）或其他与支气管痉挛相关的肺部疾病
•急性呼吸系统症状/症状（如喘息）目前使用药物治疗气道疾病，如哮喘或慢性阻塞性肺疾病
治疗后支气管痉挛的病史
已知对loxapine或阿莫沙平过敏
警告和注意事项
抗精神病药恶性综合征：可能在治疗的病人中发展服用抗精神病药物。中止治疗
低血压和晕厥：在已知患者中慎用心脑血管疾病.
癫痫发作：对有癫痫发作史的患者慎用降低癫痫发作阈值的条件.
认知和运动障碍的可能性：使用时要小心驾驶或操作机脑血管不良反应：脑卒中发病率增加老年痴呆患者短暂性脑缺血发作.
抗精神病药物治疗精神病
不良反应
最常见的不良反应（发病率大于2%，大于安慰剂）味觉障碍、镇静和咽喉刺激。
如何供应/储存和搬运
供应
AdasuVE（loxapine）吸入粉末被提供为：
ADASUVE 10毫克（NDC 1088 5-03-01）是一次性使用的一次性吸入器，包含10毫克。
loxapine，用密封的箔袋提供。AdasuVE，10毫克是用纸盒供应的。
每箱5个单位（NDC 1088～03-05）。
限制访问
AdasuVE只能通过一个被称为AdasuvE REMS的受限程序来使用。
程序[见警告和注意事项]。
储运
在室温，15°至30°C（59°至86°F）下储存（参见USP控制室）
温度。
放置在儿童接触不到的地方。
保存在袋中直到使用时间。
AdasuVE包含锂电池。根据所有联邦处理ADASUVE，国家和地方法律。
完整资料附件：https://www.adasuverems.com/AdasuveUI/rems/pdf/PrescribingInformation.pdf
ADASUVE(loxapine) inhalation powder, for oral inhalation use
INDICATIONS AND USAGE
ADASUVE®(loxapine) inhalation powder, for oral inhalation use, is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Efficacy was demonstrated in 2 trials in acute agitation: one in schizophrenia and one in bipolar I disorder.
Limitations of Use: As part of the ADASUVE Risk eva luation and Mitigation Strategy (REMS) Program to mitigate the risk of bronchospasm, ADASUVE must be administered only in an enrolled healthcare facility.
IMPORTANT SAFETY INFORMATION
WARNING: BRONCHOSPASM and
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Bronchospasm
ADASUVE can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. Administer ADASUVE only in an enrolled healthcare facility that has immediate access on site to supplies and personnel trained to manage acute bronchospasm, and ready access to emergency response services. Facilities must have a short-acting bronchodilator (eg, albuterol), including a nebulizer and inhalation solution, for the immediate treatment of bronchospasm. Prior to administering ADASUVE, screen patients regarding a current diagnosis, history, or symptoms of asthma, COPD and other lung diseases, and examine (including chest auscultation) patients for respiratory signs. Monitor for signs and symptoms of bronchospasm following treatment with ADASUVE.
Because of the risk of bronchospasm, ADASUVE is available only through a restricted program under a Risk eva luation and Mitigation Strategy (REMS) called the ADASUVE REMS.
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. ADASUVE is not approved for the treatment of patients with dementia-related psychosis.
ADASUVE is contraindicated in patients with the following:
Current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), or other lung disease associated with bronchospasm
Acute respiratory signs/symptoms (eg, wheezing)
Current use of medications to treat airways disease, such as asthma or COPD
History of bronchospasm following ADASUVE treatment
Known hypersensitivity to loxapine or amoxapine. Serious skin reactions have occurred with oral loxapine and amoxapine
ADASUVE must be administered only by a healthcare professional
Prior to administration, all patients must be screened for a history of pulmonary disease and examined (including chest auscultation) for respiratory abnormalities (eg, wheezing)
Administer only a single 10 mg dose of ADASUVE within a 24-hour period by oral inhalation using the single-use inhaler
After ADASUVE administration, patients must be monitored for signs and symptoms of bronchospasm at least every 15 minutes for at least 1 hour
ADASUVE can cause sedation, which can mask the symptoms of bronchospasm
Antipsychotic drugs can cause a potentially fatal symptom complex called Neuroleptic Malignant Syndrome (NMS), manifested by hyperpyrexia, muscle rigidity, altered mental state, irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia. Associated features can include escalated serum creatine phosphokinase (CPK) concentration, rhabdomyolysis, elevated serum and urine myoglobin concentration, and renal failure. If NMS occurs, immediately discontinue antipsychotic drugs and other drugs that may contribute to the underlying disorder, monitor and treat symptoms, and treat any concomitant serious medical problems
ADASUVE can cause hypotension, orthostatic hypotension, and syncope. Use with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that would predispose patients to hypotension. In the presence of severe hypotension requiring vasopressor therapy, epinephrine should not be used
ADASUVE may increase the risk of falls, which could cause fractures or other injuries. Patients taking antipsychotics with certain health conditions or those on long-term therapy should be eva luated by their healthcare professional for the potential risk of falls
Use ADASUVE with caution in patients with a history of seizures or with conditions that lower the seizure threshold. ADASUVE lowers the seizure threshold. Seizures have occurred in patients treated with oral loxapine, and can also occur in epileptic patients
Use caution when driving or operating machinery. ADASUVE can impair judgment, thinking, and motor skills
The potential for cognitive and motor impairment is increased when ADASUVE is administered concurrently with other CNS depressants
Treatment with antipsychotic drugs caused an increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis; ADASUVE is not approved for the treatment of patients with dementia-related psychosis
Use of ADASUVE may exacerbate glaucoma or cause urinary retention
The most common adverse reactions (incidence ≥2% and greater than placebo) in clinical studies in patients with agitation treated with ADASUVE were dysgeusia, sedation, and throat irritation
Pregnancy Category C. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk of extrapyramidal and/or withdrawal symptoms after delivery. ADASUVE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Nursing mothers: Discontinue drug or nursing, taking into account the importance of the drug to the mother
The safety and effectiveness of ADASUVE in pediatric patients have not been established