ADASUVE (loxapine) aerosol, powder
[Alexza Pharmaceuticals, Inc.]
Pharmacological Class:
Dibenzoxazepine.
Active Ingredient(s):
Loxapine 10mg; powder for oral inhalation.
Company
Teva Pharmaceuticals
Indication(s):
Acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Limitations of use: must be administered only in an enrolled healthcare facility.
Pharmacology:
The mechanism of action in the treatment of agitation associated with schizophrenia and bipolar I disorder is unknown. However, the efficacy of loxapine could be mediated through a combination of antagonism of central dopamine D2 and serotonin 5-HT2A receptors.
Clinical Trials:
The efficacy of Adasuve in the acute treatment of agitation associated with schizophrenia or bipolar I disorder was established in two short-term (24-hour), randomized, double-blind, placebo-controlled, fixed-dose trials.
Study 1 (N=344) included patients who met DSM-IV criteria for schizophrenia and Study 2 (N=314) included patients who met DSM-IV criteria for bipolar I disorder, manic or mixed episodes with or without psychotic features. The primary efficacy endpoint in both trials was the mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) score, assessed 2 hours post-dose. The key secondary endpoint was the mean Clinical Global Impression Improvement (CGI-I) Scale score at two hours.
In both studies, treatment with Adasuve was statistically significantly superior to placebo on the mean change in PEC score at 2 hours (Study 1: -8.7, 95% CI -2.9 [-4.2, -1.6]; P<0.0001 and Study 2: -9.2, 95% CI -4.5 [-5.8, -3.1]; P<0.0001). The decrease in agitation with Adasuve was apparent at each time point tested (10, 20, 30, 45, 60, 90, and 120 minutes post-dose).
For more clinical trial results, see full labeling.
Legal Classification:
Rx
Adults:
10mg by oral inhalation using a single-use inhaler. Administer only a single dose within a 24 hour period. Prior to administration, screen for current diagnosis or history of asthma, COPD, other lung diseases, and examine for respiratory abnormalities. Monitor for signs/symptoms of bronchospasm and perform a physical exam at least every 15 minutes for at least one hour after administration.
Children:
Not established.
Contraindication(s):
Current diagnosis or history of asthma, COPD, or other lung disease associated with bronchospasm. Acute respiratory signs/symptoms (eg, wheezing). Concomitant drugs to treat airways disease (eg, asthma, COPD). History of bronchospasm after Adasuve treatment. Amoxapine sensitivity.
Warnings/Precautions:
Risk of bronchospasm. Must be administered by a healthcare personnel in facility that has immediate access to manage acute bronchospasm. Increased mortality in elderly patients with dementia-related psychosis (not approved use). Monitor for neuroleptic malignant syndrome. Cardio- or cerebrovascular disease. Conditions that predispose to hypotension (eg, dehydration, hypovolemia, or concomitant antihypertensive drugs). History of seizures. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester of pregnancy). Pregnancy (Category C). Nursing mothers: not recommended.
Interaction(s)
Additive effects with concomitant other anticholinergics (eg, antiparkinson drugs) or other CNS depressants (eg, alcohol, opioids, benzodiazepines, tricyclic antidepressants, general anesthetics, phenothiazines, sedative/hypnotics, muscle relaxants); consider reducing dose of these drugs.
Adverse Reaction(s)
Dysgeusia, sedation, throat irritation; hypotension, syncope, lowered seizure threshold, anticholinergics effects (eg, glaucoma, urinary retention).
Notes:
Available only through a restricted program under Adasuve REMS. Call (888) 970-7367 or visit www.adasuverems.com to enroll.
How Supplied:
Single-use, disposable inhaler—5
LAST UPDATED:
11/12/2013
FDA批准洛沙平治疗精神分裂症和双相障碍
美国食品和药物管理局（FDA）批准洛沙平（Adasuve，Alexza制药公司）吸入粉剂10 mg用作精神分裂症或1型双相障碍成人伴随的激动的急性治疗。
据估计，美国目前有320万例患者接受精神分裂症或1型双相障碍治疗，其中约90%在他们的病程期间将发生躁动。
这些患者每年平均有11-12次躁动发作。
Adasuve综合了抗精神病药物洛沙平与该公司的专利Staccato给药系统。
“Adasuve是首个被批准用于精神分裂症和双相障碍成人躁动急性治疗的非注射疗法。”Thomas King（美国加州Mountain ViewAlexza制药公司董事长和首席执行官）在一场新闻发布会上说。
“我们认为，快速和无创给药的能力将对患者和治疗他们的医务人员非常重要。”
FDA根据包括1600名患者和对照参与者的临床数据，批准了洛沙平吸入粉剂上市。
在2项3期试验中（1项精神分裂症研究和1项1型双相障碍研究），洛沙平吸入粉剂10 mg达到主要有效性终点，给药后2小时显示与安慰剂相比躁动减少具有统计学意义。
该药物起效也迅速，给予活性治疗后10分钟观察到躁动减少具有统计学意义。
洛沙平可导致支气管痉挛，而支气管痉挛可导致哮喘或慢性阻塞性肺疾病（COPD）患者呼吸窘迫或心搏骤停。
该药还带有警告：痴呆相关精神病老年患者具有支气管痉挛和死亡率增加的风险。
鉴于该药具有导致严重不良事件的可能性，洛沙平吸入粉剂10 mg仅可通过有限制的计划得到，而且必须在风险评估和缓解策略（Adusuve REMS）下进行。
该药物也只能在可以立即获得设备及受过急性支气管痉挛治疗培训（包括高级气道管理）的人员的医疗保健机构中使用。
洛沙平吸入粉剂10 mg未被批准用于治疗痴呆相关精神病患者，禁用于当前被诊断为哮喘、COPD或其他伴有支气管痉挛的肺疾病或有上述疾病病史的患者。
该药也禁用于有急性呼吸系统体征或症状的患者，以及禁用于正在使用治疗哮喘或COPD等气道疾病的药物的患者。
有用该药治疗后支气管痉挛病史的患者也不应该接受洛沙平吸入粉剂10 mg治疗。
Adasuve由美国加州Mountain ViewAlexza制药公司生产。