ST LOUIS (MD Consult) - On July 31, 2009, Janssen announced that the US Food and Drug Administration (FDA) has approved Invega Sustenna (paliperidone palmitate) extended-release suspension for the acute and maintenance treatment of schizophrenia in adults. Invega Sustenna is an injectable, long-acting, atypical antipsychotic that is administered once monthly.

According to Henry A. Nasrallah, MD, a clinical investigator who worked on the Invega clinical trials, and a professor of psychiatry and neuroscience at the University of Cincinnati College of Medicine, "Inconsistent compliance with medications is arguably one of the single greatest impediments to managing the symptoms of schizophrenia and delaying the time to relapse. The approval of once-monthly Invega Sustenna will provide health care professionals with a treatment option that is, at the same time, a definitive monitoring tool for uninterrupted medication compliance, which may help optimize clinical outcomes in schizophrenia."

This FDA approval was granted on the basis of data from 4 acute symptom control studies and a longer-term maintenance study that compared Invega Sustenna with placebo. Invega Sustenna was shown to be superior to placebo in improving positive and negative syndrome scale (PANSS) total scores in the acute treatment trials, and shown to significantly delay time to relapse (vs placebo) in the longer-term maintenance study.

In clinical trials, the most common adverse events (incidence ≥5% and occurring at least twice as often as placebo) were injection-site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder. Rare, but serious, adverse effects that have occurred with patients receiving Invega Sustenna include neuroleptic malignant syndrome and tardive dyskinesia.

Invega Sustenna is available in milligrams of paliperidone palmitate in dose strengths of 39, 78, 117, 156, and 234 mg. Clinical trial data presented at medical meetings were often reported as milligram equivalents to paliperidone. Each dose of paliperidone palmitate is equivalent to a specific dose of paliperidone (39, 78, 117, 156, and 234 mg of paliperidone palmitate are equivalent to 25, 50, 75, 100, and 150 mg of paliperidone, respectively). The prefilled syringes require no reconstitution or refrigeration. Patients initiate treatment with 2 injections administered in the deltoid muscle 1 week apart (day 1 at 234 mg and day 8 at 156 mg), followed by injections every month thereafter administered in either the deltoid or gluteal muscle.

 

圣路易斯(MD Consult)——2009年7月31日，杨森制药公司宣布，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。

参加Invega临床试验的临床研究员、辛辛那提州立大学医学院精神病学与神经系统科学教授Henry A. Nasrallah博士表示，“对药物治疗依从性差是治疗精神分裂症症状、推迟复发时间的单个最严重的制约因素之一。批准Invega Sustenna 每月一次用药不仅会为医护人员提供一种治疗选择，而且同时还可以作为监测患者药物治疗依从性有无间断的可靠手段，这可能有助于优化精神分裂症的临床治疗效果。”

FDA的这条批准令是基于4项急性症状控制研究和1项较长期的Invega Sustenna与安慰剂维持治疗比较研究的数据。紧急救治试验表明，Invega Sustenna在改善阳性和阴性症状量表(PANSS)总评分方面优于安慰剂，而在较长期的维持治疗研究中，与安慰剂对照相比，该药可显著推迟复发时间。

在临床试验中，最常见的不良事件(发生率≥5%且发作频率至少为安慰剂的2倍)为注射部位反应、嗜睡/镇静、眩晕、静坐不能以及锥体外系功能障碍。在接受Invega Sustenna治疗的患者中发生少但很严重的不良反应有抗精神病药恶性综合征和迟发型运动障碍。

市售的Invega Sustenna是以毫克计的棕榈酸帕潘立酮，包括39、78、117、156及234 mg这几种剂量强度规格。医学会议上提供的临床试验数据常以帕潘立酮的毫克当量报告。各个剂量的棕榈酸帕潘立酮均相当于一定剂量的帕潘立酮(39、 78、117、156及234 mg的棕榈酸帕潘立酮分别相当于25、50、 75、100及 150 mg的帕潘立酮)。预注满药品的注射器无需再作调整或冷藏。患者的初始治疗方案为三角肌内注射2次，中间间隔1w(第1d为234mg，第8d为156mg)，此后每月注射一次，选择三角肌或臀大肌注射均可。