2015年4月28日美国食品和药品监管局(FDA)批准第一个仿制版本Abilify (阿立哌唑[aripiprazole])。仿制阿立哌唑是一个非典型抗精神药被批准治疗精神分裂症和躁狂抑郁性精神病。
Alembic Pharmaceuticals Ltd.，Hetero Labs Ltd.，Teva Pharmaceuticals和Torrent Pharmaceuticals Ltd四家公司已接到FDA批准上市仿制阿立哌唑在多种规格和剂型。
FDA的药品评价和研究中心仿制药办公室代理主任John Peters，M.D.说：“对有长期健康情况患者拥有获得治疗是很重要的，”“卫生保健专业人员和消费者可被确保FDA-批准的仿制药具有品牌药符合相同的严格标准。”
精神分裂症是一种慢性，严重和失能脑疾病。约1%美国人有此病。典型地，是在小于30岁成年首先见到症状。精神分裂症的症状包括幻听，相信其他人都在阅读他们的头脑或控制他的思想和被怀疑或撤出。
躁狂抑郁性精神病，也称为躁狂抑郁症，是另一类脑病致非寻常情绪，精力，活动水平和能力进行日常任务。躁狂抑郁性精神病的症状包括抑郁和高度或急躁情绪的变换期，增加活动性和躁动，胡思乱想，说话快，冲动行为和睡眠需求减低。
所有费典型性抗精神病药含一个黑框警告警戒卫生保健专业人员关于伴随离开说明书使用这些药物治疗行为问题在老年痴呆症相关的精神病中增加死亡风险。没有被批准药物治疗老年痴呆症相关的精神病患者。
阿立哌唑的黑框警告还警告关于在儿童，青少年，和年轻成年中服用抗抑郁药自杀想法和行为的风险增加。患者应被监视自杀思想和行为的恶化和出现。阿立哌唑必须随一个患者用药指南一起被分发指南描述关于药物使用和风险重要信息。
在对Abilify临床试验中，服用Abilify成年报告最常见副作用是恶心，呕吐，便秘，头痛，眩晕，可能控制的肢体和身体运动(静坐不能)，焦虑，失眠，和躁动。
被FDA批准的仿制处方药有与品牌药相同的高质量和强度。仿制处方药制造和包装地点必须通过与其品牌药相同质量标准。
www.oneyao.net
www.120ty.net
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm444862.htm
New Drugs Online Report for aripiprazole
Information
Generic Name: aripiprazole
Trade Name: Abilify Maintena
Synonym: OPC-14597
Entry Type: New formulation
Development and Regulatory status
UK: Launched
EU: Launched
US: Launched
UK launch Plans: Available only to registered users
Actual UK launch date: January 2014
Comments
Mar 15: EU CHMP issues a positive opinion for a pre-filled dual chamber syringe kit to administer Abilify Maintena for the maintenance treatment of schizophrenia. Reconstitution occurs within the pre-filled dual chamber syringe, in a single step, which allows for easier handling [17].
02/04/2015 09:25:55
Mar 15: Deltoid muscle approved in the EU as a new injection site for Abilify Maintena [17].
02/04/2015 09:25:04
Sep 14: US FDA approves a new formulation of Abilify Maintena – a pre-filled dual-chamber syringe. Launch is planned for Jan 2015 [16].
03/10/2014 13:59:53
Jan 14: Launched in UK.
27/03/2014 12:52:25
Abilify Maintena was launched in the US in March 13 [14].
21/11/2013 12:30:52
Nov 13: Approved in the EU [13].
21/11/2013 12:27:51
Sep 13: EU positive opinion for Abilify Maintena for the maintenance treatment of schizophrenia in adults stabilised with oral aripiprazole [12].
20/09/2013 15:16:03
Mar 13: Approved in the US as Abilify Maintena. Otsuka and Lundbeck plan to jointly market in the US, with availability expected on March 18. [11].
03/03/2013 15:36:05
Dec 12: Once monthly depot preparation filed in the EU for the maintenance treatment of adult patients with schizophrenia [10].
24/12/2012 09:16:01
Sept 12: US FDA is to review a resubmission of a new drug application for aripiprazole depot for treating schizophrenia. A decision on approval is expected by Feb 28 2013. [9]
17/09/2012 16:36:32
Jul 12: FDA has issued a complete response letter citing deficiencies from a recent inspection of a third-party supplier of sterile water [8].
31/07/2012 21:41:39
Nov 11: Once-monthly aripiprazole depot filed in the US for the indication of maintenance treatment of schizophrenia in adults [6].
24/11/2011 21:56:57
Mar 11: Filing anticipated during 2011 [2]
21/03/2011 14:42:22
Trial or other data
Jun 14: PIII NCT00706654 study (n=662) published in Br J Psych. 400mg ARP once-monthly depot was non-inferior to oral ARP (impending relapse rates at wk 26: 7.12% depot vs. 7.76% oral (difference: –0.64%, 95% CI –5.26-3.99, excluded predefined non-inferiority margin of 11.5%) [15].
13/06/2014 10:37:09
May 12: PIII study presented at the 2012 American Psychiatric Association Annual Meeting. The multicentre study included 710 adults with schizophrenia who required chronic treatment with an antipsychotic. It comprised four phases: 1) an oral conversion phase (4-6 wks; pts not currently being treated with aripiprazole were converted to oral aripiprazole monotherapy); 2) an oral stabilisation phase (4-12 wks; all pts treated with oral aripiprazole until achieving pre-specified stability criteria for at least 4 wks; 3) an IM depot formulation stabilisation phase (pts received aripiprazole IM depot formulation injections every four wks, with co-administration of oral aripiprazole during the first two wks; n=576); and 4) a maintenance treatment phase. In the latter phase, pts participating in phase 3 of the study who met stability criteria for 12 wks (n=403) were randomised to double-blind treatment with IM aripiprazole (n=269) or placebo (n=134) once every 4 wks for 52 weks. Aripiprazole IM delayed time-to-impending relapse vs. placebo (HR 5.03, p<0.0001). The rate of impending relapse was lower with aripiprazole IM depot formulation vs. placebo after 52 wks of treatment (10.0% vs. 39.6%, respectively; p<0.0001). PANSS subscale scores showed both positive & negative symptom stability with aripiprazole IM depot formulation but significant worsening for pts who received placebo [mean change from baseline in PANSS positive symptom subscale scores was 0.4 for aripiprazole IM & 4.3 for placebo [p<0.0001]); and a mean change in baseline of 0.2 vs. 1.6 for PANSS negative subscale scores [p<0.0001]]. Mean change from baseline in Personal & Social Performance scale scores showed greater stability of social functioning with aripiprazole IM depot formulation vs. placebo (-1.7 vs. -6.2, respectively; p=0.0002). Mean change from baseline in the Investigator’s Assessment Questionnaire (a 12-item assessment of overall effectiveness) total scores also remained more stable amongst pts who received aripiprazole IM (mean change of +1.3 vs. +3.8 for placebo; p<0.0001). The most common treatment-emergent adverse events during the maintenance phase included insomnia (10.0% vs. 9.0%); tremor (5.9% vs. 1.5%); & headache (5.9% vs. 5.2%). The incidence of clinically relevant weight gain (>7% increase from baseline) was 6.4% for aripiprazole IM & 5.2% for placebo. Discontinuation rates due to treatment-related adverse events were 7.1% for aripiprazole IM depot formulation vs. 13.4% for placebo [7].
10/05/2012 08:55:26
Otsuka Pharmaceuticals and H. Lundbeck announced today that the FDA has determined that a new drug application for once-monthly aripiprazole depot formulation for the indication of maintenance treatment of schizophrenia in adults is sufficiently complete to permit a substantive review [5].
23/11/2011 11:17:57
Nov 11: Lundbeck and Otsuka are collaborating on a number of pipeline agents including depot aripiprazole. If licensed, Lundbeck will get half of the sales of the new treatment in the EU and Canada one fifth of the sales in the US [4].
14/11/2011 15:49:19
Sep 11: NCT01432444 – a PIII open-label study to compare retrospective hospitalization rates of patients with schizophrenia treated with oral antipsychotics to prospective hospitalization rates of these patients treated with IM depot aripipriazole. The study will start in Sep 11, will enrol about 500 patients and is due to complete Apr 13. Patients will be given 400mg aripipriazole IM depot every 26-30 days (may be adjusted at the investigator´s discretion to 300mg) for 6 injections. Subjects have the option of entering the extension phase of the study and continuing with injections until the drug is either commercially available, or December 2013 [3].
20/09/2011 10:41:17
Oct 10: An independent data monitoring committee (IDMC) has recommended the early termination of the PIII 52-week, placebo-controlled Aripiprazole Intramuscular Depot Study in Schizophrenia-U.S (31-07-246) as it successfully met efficacy criteria at a protocol-specified interim analysis. The study incorporated two interim analyses, at 50% and 75% of the 125 events needed to complete the study. It was determined that 50% of the events were achieved in June, seven months ahead of schedule [1].
08/10/2010 13:23:29
Oct 10: Aripiprazole IM depot is a sterile lyophilized cake that when reconstituted with sterile water for injection forms an injectable suspension. The Aripiprazole Intramuscular Depot Study in Schizophrenia-U.S evaluated this formulation as a once-monthly injection for the maintenance treatment of schizophrenia [1].
08/10/2010 13:23:14
Evidence Based Evaluations
AWMSG http://www.awmsg.org/awmsgonline/app/appraisalinfo/909
NICE (MPC) http://www.nice.org.uk/Advice/ESNM39
SMC https://mail.miaa.nhs.uk/owa/redir.aspx?C=MMmfcw8120-va6XNcGX_xQU9naMYQtEIH9U-2CiY2h52XC-_INEM1_CQeKOFVDiW0i05ekC-8RE.&URL=http%3a%2f%2fwww.scottishmedicines.org.uk%2ffiles%2fadvice%2faripiprazole_Abilify_FINAL_April_2014_for_website.pdf
EPAR http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002755/human_med_001711
.jsp&mid=WC0b01ac058001d124
References
Available only to registered users
Category
BNF Category: Antipsychotic depot injections (04.02.02)
Pharmacology: Atypical antipsychotic - dopamine D2 receptor agonist, serotonin 5HT1A/2C receptor agonist & serotonin 5HT2A/7 receptor antagonist
Epidemiology: An English study reported an incidence of 15.2 per 100,000 person-years. A systematic review reported a prevalence of 7.2/1,000 persons. In children and adolescents between the ages of 5 and 18 the prevalence has been estimated to be 0.4%. It can develop at any age but starts most commonly in adolescence and the early 20s. In young people aged 10-18 it accounts for 24.5% of all psychiatric admissions, with a marked rise after the age of 15 [18].
Indication: Schizophrenia
Additional Details: IM depot injection (powder plus solvent / prefilled dual chamber syringe kit) - maintenance treatment
Method(s) of Administration
Intramuscular
Company Information
Name: Lundbeck
US Name: Otsuka
Further Information
Anticipated commissioning route (England) CCG
High cost drug list? Awaiting Update
Implications Available only to registered users