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2014年9月10日，美国食品药品监督管理局(FDA)批准Contrave(盐酸纳曲酮[naltrexone hydrochloride]和盐酸安非他酮，bupropion hydrochloride 缓释片)作为慢性体重处理除减低-热量饮食和体力活动外治疗选择。
药物被批准为使用在成年有体重指数(BMI)30或更大(肥胖)或成年有BMI 2或更大(超重)至少有一种体重-相关情况例如高血压，2型糖尿病，或高胆固醇(血脂异常)。
BMI，基于个体的体重和身高测量机体脂肪，被用于确定肥胖和超重类型。按照美国疾病控制和预防中心，在美国超过三分之一成年是肥胖。
FDA药品评价和研究中心代谢和内分泌产品部主任Jean-Marc Guettier，医学博士说：“肥胖继续是主要公共卫生关注，”“当使用作为制定与健康生命方式包括减低-热量饮食和锻炼，对慢性体重处理超重和有至少抑制体重-相关健康情况Contrave对肥胖或人们提供另一种治疗选择。”
Contrave是两种FDA-已批准药物，纳曲酮和安非他酮的组合，一抑制缓释制剂。纳曲酮被批准治疗乙醇和阿片依赖性。安非他酮被批准治疗抑郁和季节性情感障碍和帮助停止吸烟治疗。
在多个临床试验包括约4,500肥胖和超重患者有和无显著体重-相关情况治疗共一年中评价Contrave的有效性。所有患者接受生活方式修改有减低热量饮食和有规律体育活动组成。
来自一项临床试验纳入无糖尿病患者显示患者有平均丧失体重4.1%经历治疗与安慰剂(无活性药丸)在一年时。在这项试验中，用Contrave治疗患者42 %丢失其体重至少5%与用安慰剂治疗比较有17 %。来自另一项临床试验纳入有2型糖尿病患者结果显示在一年时患者有平均体重丢失超过安慰剂2 %。在这项试验中，用Contrave治疗患者36 %丢失其体重至少5 %与之比较用安慰剂治疗患者为18 %。.
患者用维持剂量Contrave应在12周后评价测定治疗是否起作用。如果一例患者没有丢失基线体重的至少5 %，应终止Contrave，因为用继续治疗患者将不可能实现和持续临床有意义体重丢失。
因为含安非他酮，Contrave有一个黑框警告警戒卫生保健专业人员和患者伴随抗抑郁药物自杀想法和行为风向增加。这个警告还注释用安非他酮为停止吸烟患者中曾报道严重神经精神事件。
Contrave可能致癫痫发作和有癫痫发作疾病患者中必须不使用。癫痫发作的风险是剂量相关。当正在用Contrave治疗经受癫痫发作患者中Contrave应被终止和不再开始。
Contrave还可能升高血压和心率和有未控制高血压患者中必须不使用。用Contrave治疗观察到血压和心率增加的临床意义不清楚，特别是对有心脏相关和脑血管患者(血管功能失常影响脑)病，因为临床试验排除在以前6个月心脏发作或卒中史，危及生命心律失常，或充血性心衰患者。药物开始前应测量血压和脉搏和在规则间隔应监视，尤其是患者治疗以前控制高血压。
其他含安非他酮产品不应与Contrave一起使用。有吃疾病患者(贪食症或神经性厌食症)不应使用药物。用阿片类或治疗对阿片依赖性患者，或正在经受急性阿片撤药患者不应使用Contrave。正在突然终止酒精，苯二氮卓类，巴比妥类和抗癫痫类药丸患者不应用Contrave。妊娠或试图成为妊娠妇女不应用Contrave。
用Contrave报道最常见不良反应包括恶心，便秘，头痛，呕吐，眩晕，失眠，口干，和腹泻。.
FDA 曾在要求以下上市后要求：
⑴一项心血管结局试验评估伴Contrave使用心血管风险；
⑵在儿童患者中两项疗效，安全性，和临床药理学研究(一项在12至17岁患者，和一项在7至11岁患者)；
⑶一项非临床(动物)幼年毒性研究特别集中在生长和发育以及行为，学习，和记忆；
⑷一项研究评价Contrave对心脏传导的影响；
⑸临床试验评价在有肝或肾受损患者中给药；
⑹一项临床试验评价Contrave和其他药物间相互作用潜能。
Contrave由伊利诺伊州迪尔菲尔德武田Takeda制药美国公司，加州拉霍亚Orexigen 治疗药公司分发。
Generic Name: bupropion hydrochloride and naltrexone hydrochloride
Date of Approval: September 10, 2014
Company: Orexigen Therapeutics
Treatment for: Obesity
CONTRAVE Rx
Pharmacological Class:
Opioid antagonist + aminoketone.
Active Ingredient(s):
Naltrexone HCl, bupropion HCl 8mg/90mg; extended-release tablets.
Company
Takeda Pharmaceuticals North America, Inc.
Indication(s):
Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30kg/m2 or ≥27kg/m2 in the presence of at least one weight-related comorbidity (eg, hypertension, type 2 diabetes, or dyslipidemia). Limitations of use: effect on cardiovascular morbidity and mortality has not been established. Safety and efficacy in combination with other weight loss products, including Rx or OTC drugs, and herbal preps, have not been established.
Pharmacology:
Contrave combines naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine.
Legal Classification:
Rx
Adults:
Swallow whole. Avoid high-fat meals. Escalate dose gradually. ≥18 years: Week 1: 1 tab daily in the AM; Week 2: 1 tab daily in the AM and 1 tab daily in the PM; Week 3: 2 tabs in the AM and 1 tab in the PM; Week 4 and thereafter: 2 tabs in the AM and 2 tabs in the PM. Max 32mg/360mg per day. Evaluate response after 12 weeks. Discontinue if ≥5% weight loss is not achieved. Concomitant CYP2B6 inhibitors (eg, ticlopidine, clopidogrel), moderate or severe renal impairment: max 2 tabs daily (1 tab each AM & PM). Hepatic impairment: max 1 tab in the AM.
Children:
<18 years: not recommended.
Contraindication(s):
Uncontrolled hypertension. Seizure disorder. Concomitant other bupropion-containing products. Bulimia. Anorexia nervosa. Use of chronic opioid or opiate agonist (eg, methadone), or partial agonists (eg, buprenorphine). Acute opiate withdrawal. Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptics. During or within 14 days of discontinuing MAOIs. Concomitant linezolid or IV methylene blue. Pregnancy (Category X).
Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor for clinical worsening or unusual behavioral changes in all patients. Monitor for neuropsychiatric reactions. Increased risk of seizures with predisposing risk factors (eg, history of head trauma, prior seizure, severe stroke, arteriovenous malformation, CNS tumor or infection, others: see full labeling); discontinue if seizure occurs and do not restart. Diabetes. Hypoglycemia. Cardiac or cerebrovascular disease. Monitor BP, pulse, and blood glucose levels prior to starting and during treatment. Risk of hepatic injury; discontinue if signs/symptoms of acute hepatitis occur. Screen for bipolar disorder. Angle-closure glaucoma. Elderly. ESRD, nursing mothers: not recommended.
Interaction(s)
See Contraindications. Vulnerability to opioid overdose with concurrent opioid analgesics; if chronic therapy needed, discontinue Contrave. To prevent precipitation of withdrawal: discontinue chronic opioids 7–10 days prior to initiation. Reduced benefit with opioid-containing drugs (eg, antitussives, antidiarrheals, analgesics). May be potentiated by CYP2B6 inhibitors (see Adults). Avoid concomitant CYP2B6 inducers (eg, ritonavir, lopinavir, efavirenz). Caution with CYP2D6 substrates (eg, tricyclics, SSRIs, antipsychotics [eg, haloperidol, risperidone, thioridazine], β-blockers [eg, metoprolol], Class 1C antiarrhythmics [eg, propafenone, flecainide]); consider dose reduction (esp. drugs with a narrow therapeutic index). Caution with drugs that lower seizure threshold (eg, antipsychotics, antidepressants, theophylline, steroids). Monitor for CNS toxicity with levodopa, amantadine. Avoid alcohol. May potentiate OCT2 substrates (eg, amantadine, amiloride, cimetidine, dopamine, famotidine, memantine, metformin, pindolol, procainamide, ranitidine, varenicline, oxaliplatin); monitor. Concomitant antidiabetics; adjust dose if hypoglycemia develops. May cause false (+) test results in urine immunoassay for amphetamines.
Adverse Reaction(s)
Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea; allergic reactions.
How Supplied:
Tabs—120
LAST UPDATED:
12/9/2014
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf |
