近日，美国食品药品监督管理局FDA批准缓释悬浮液/注射剂Aristada(月桂酰阿立哌唑)，用于治疗精神分裂症成人患者。Aristada经臂部或臀部注射给药，每4-6周给药一次。
“精神分裂症长效治疗药物可以改善患者的生活，”FDA药物评估研究中心精神病药品部门主任Mitchell Mathis博士称。“能够获得各种治疗方法和不同的给药剂量形式，对于精神病患者而言至关重要，治疗方案也因此可满足患者需求。”
批准日期：2015年10月5日  公司：Alkermes公司
ARISTADA™（阿立哌唑lauroxil）缓释注射悬浮液，供肌肉注射使用
美国首次批准：2015年
警告：死亡率增加老年痴呆相关精神病见完整的黑框警告完整的处方信息。
老年痴呆患者的相关精神病用抗精神病药物治疗是在死亡的风险增加。
ARISTADA未被批准用于治疗老年痴呆症相关的精神病治疗。
适应症和用法
ARISTADA是精神分裂症的治疗中所表示的非典型抗精神病药。
用法用量
通过注射在三角肌肌肉注射给药（441毫克剂量只）或医疗专业人士臀（441毫克，662毫克或882毫克）的肌肉。
对于患者天真的阿立哌唑，建立耐受口服阿立哌唑，然后与ARISTADA开始治疗。
ARISTADA可在441毫克剂量开始，662毫克或882毫克的施用每月或882毫克的剂量每6周。
与第一ARISTADA注射的同时，实施治疗用口服阿立哌唑，连续21天。
可能需要错过剂量给药方案进行调整。
所需的1）已知的CYP2D6弱代谢和2）进行拍摄CYP3A4抑制剂，CYP2D6抑制剂或CYP3A4诱导为2周以上患者调整剂量。
剂型和规格
对于延长释放可注射悬浮液：441毫克，662毫克或882毫克单次使用的预先填充的注射器
禁忌
已知过敏阿立哌唑
警告和注意事项
脑血管不良反应的老年痴呆相关精神病：增加脑血管的不良反应发生率（如中风，短暂性脑缺血发作，包括死亡）。
抗精神病药物恶性症候群：与管理立即停止，并密切监测。
迟发性运动障碍：如临床适宜以停止。
代谢的变化：监测高血糖，血脂异常，和体重增加。
体位性低血压：监控心脏速率和血压和警告患者具有已知的心血管或脑血管疾病，和脱水或晕厥的风险。
白细胞减少症，中性粒细胞减少，粒细胞缺乏症和：执行在患者全血计数与临床显著低白细胞（WBC）计数的历史。考虑停药，如果临床显著下降，白细胞在没有其他致病因素。
癫痫发作：患者谨慎使用有惊厥史或与降低癫痫发作阈值的条件。
潜在的认知和运动功能障碍：操作机械设备时要小心。
不良反应
最常观察到的不良反应与ARISTADA（发生率≥5％和至少两次，对于安慰剂）是静坐不能。
特殊人群中使用
怀孕：可在妊娠的第三孕期暴露的女性新生儿引起锥体外系和/或戒断症状。
包装规格
ARISTADA 441MG PFS 1  ARIPIPRAZOLE LAUROXIL     65757-0401-03 
ARISTADA 662MG PFS 1  ARIPIPRAZOLE LAUROXIL     65757-0402-03 
ARISTADA 882MG PFS 1  ARIPIPRAZOLE LAUROXIL     65757-0403-03

ARISTADA(aripiprazole lauroxil) extended-release injectable suspension, for intramuscular use

Initial U.S. Approval: 2015
ARISTADA is indicated for the treatment of schizophrenia.
Generic Name
Aripiprazole lauroxil
Strengths
441mg, 662mg, 882mg
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. ARISTADA is not approved for the treatment of patients with dementia-related psychosis. Important Safety Information continued below.
Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.
Cerebrovascular Adverse Reactions, Including Stroke: Increased incidence of cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, have been reported in placebo-controlled trials of elderly patients with dementia-related psychosis treated with risperidone, aripiprazole, and olanzapine. ARISTADA is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as NMS may occur with administration of antipsychotic drugs, including ARISTADA. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. Discontinue ARISTADA if clinically appropriate. There is no known treatment for established TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include:
•Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with oral aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug.
•Dyslipidemia: Undesirable alterations in lipids 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: Aripiprazole may cause orthostatic hypotension which can be associated with dizziness, lightheadedness, and tachycardia. Monitor heart rate and blood pressure, and warn patients with known cardiovascular or cerebrovascular disease and risk of dehydration and syncope.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported. Patients with a history of clinically significant low white blood cell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) during the first few months of receiving ARISTADA. Consider discontinuation of ARISTADA at the first sign of a clinically significant decline in WBC count in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue ARISTADA in patients with severe neutropenia (absolute neutrophil count <1000/mm3) and follow their WBC until recovery.
Seizures:
ARISTADA should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: ARISTADA may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain ARISTADA does not affect them adversely.
Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Advise patients regarding appropriate care in avoiding overheating and dehydration. Appropriate care is advised for patients who may exercise strenuously, may be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or are subject to dehydration.
Dysphagia:
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use; use caution in patients at risk for aspiration pneumonia.
Concomitant Medication: Decreasing the ARISTADA dosage is recommended in patients taking strong CYP3A4 inhibitors and/or strong CYP2D6 inhibitors for longer than 2 weeks. Increasing the ARISTADA dosage is recommended in patients taking CYP3A4 inducers for longer than 2 weeks. No ARISTADA dosage changes are recommended for patients taking CYP450 modulators for less than 2 weeks.
Most Commonly Observed Adverse Reaction: The most common adverse reaction (≥5% incidence and at least twice the rate of placebo in patients treated with ARISTADA) was akathisia.
Injection-Site Reactions: Injection-site reactions were reported by 4%, 5%, and 2% of patients treated with 441 mg ARISTADA, 882 mg ARISTADA, and placebo, respectively. Most of these were injection-site pain and associated with the first injection and decreased with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) occurred at less than 1%.
Dystonia:
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first days of treatment and at low doses.
Pregnancy/Nursing: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider of a known or suspected pregnancy. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA during pregnancy. Aripiprazole is present in human breast milk. The benefits of breastfeeding should be considered along with the mother’s clinical need for ARISTADA and any potential adverse effects on the infant from ARISTADA or from the underlying maternal condition.
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INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
ARISTADA is indicated for the treatment of schizophrenia.
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. ARISTADA is not approved for the treatment of patients with dementia-related psychosis. Important Safety Information continued below.
Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.
Cerebrovascular Adverse Reactions, Including Stroke: Increased incidence of cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, have been reported in placebo-controlled trials of elderly patients with dementia-related psychosis treated with risperidone, aripiprazole, and olanzapine. ARISTADA is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as NMS may occur with administration of antipsychotic drugs, including ARISTADA. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. Discontinue ARISTADA if clinically appropriate. There is no known treatment for established TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include:
•Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with oral aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemi