FDA批准第一个为成年中处理非-阿片治疗阿片撤出症状

保留监管局顶优先地鼓励更广泛创新和发展安全和有效治疗对阿片使用疾患

2018年5月16日美国食品和药品监管局今天批准Lucemyra (lofexidine 盐酸)为缓解在成年中鸦片戒断症状促进突然终止。而Lucemyra可能减轻戒断症状的严重性，它可能不能完全地预防它们和仅被批准为 治疗共至14天。Lucemyra不是一种为鸦片使用疾患(OUD)治疗，但可能被使用作为一个更宽广，长期治疗为处理OUD计划的一部分.

FDA长官Scott Gottlieb，M.D说：“作为我们城内支持患者与成瘾斗争的部分，我们是致力于鼓励创新方法有助于缓解当患者终止鸦片出现的生理学挑战,‘ “我们正在开发新指导原则帮助加速更好治疗的发展，包括那些有助于处理鸦片戒断症状。我们知道对寻求帮助和最终克服成瘾患者阿片类戒断综合征的身体症状可能是最大屏障之一。惧怕经受戒断症状 往往预防那些遭受鸦片成瘾寻求帮助，和那些寻求帮助可能复发由于连续不断戒断症状。 FDA 将继续鼓励创新和治疗的发展帮助那些遭受鸦片成瘾转至清醒的生活，以及面对不幸的特征那是有时伴随使用药物辅助治疗。”

阿片类戒断综合征包括症状— 例如 焦虑，忧虑，睡眠问题，肌肉痛，流鼻涕，出汗，恶心，呕吐，腹泻和药物渴求— 发生在停止或减低鸦片的使用后在任何人有对鸦片的身体依赖性。. 身体依赖性对鸦片身体依赖性是对鸦片使用可预期的生理学反应。阿片类戒断综合征的这些症状发生在患者曽适当地处方使用鸦片和有OUD患者两者都发生。

在患者作为处方适当地使用鸦片镇痛药，阿片类戒断综合征被典型地处理通过缓慢地滴定调整药物，它是意向避免或减轻撤药的效应而允许机体适应没有鸦片。在有OUD患者中，撤药是典型地处理被另一种鸦片类药物取代处理，接着通过逐渐减低或变至用FDA-批准药物-辅助治疗药物例如美沙酮[methadone]，丁丙诺啡[buprenorphine]或纳曲酮[naltrexone] 维持治疗；或通过各种药物目标在特异性 症状，例如非处方药[over-the-counter]治疗对胃不适或周身疼痛。患者的卫生保健提供者还可能处方其他治疗。

FDA的药物评价和研究中心麻醉药，镇痛药和成瘾产品部主任Sharon Hertz，M.D说： “今天的批准代表第一次FDA-批准的非-鸦片治疗为鸦片戒断症状的处理和提供一种新选择，允许提供者与患者工作选择对一位个体需要最适宜治疗,”

Lucemyra是一种口服，选择性α2-肾上腺素能受体激动剂，它减低去甲肾上腺素的释放。在自主神经系统中去甲肾上腺素的作用被认为是在阿片类戒断综合征的症状的许多中起作用。Lucemyra的安全性和疗效 被两项866成年随机化，双盲，安慰剂对照临床试验符合诊断和统计手册-IV标准对鸦片依赖性患者支持，是对鸦片身体依赖性和正在遭受突然鸦片终止。研究利用Gossop (SOWS-Gossop)的短鸦片戒断症状评分评价获益，它是一个患者-报告的结局仪器评估鸦片戒断症状. 。这些症状包括感觉不适，胃痉挛，肌肉痉挛/抽搐，冷的感觉，心怦怦跳动，肌肉紧张，周身疼痛，打呵欠，流泪和失眠/睡眠问题。

对每一种阿片类戒断综合征症状，患者被要求利用四个反应选择(无，轻，中度和严重)对他们的症状严重程度计分，用SOWS-Gossop总评分范围从0至 30计分，其中一个较高评分表明一个较大的戒断症状严重程度。SOWS-Gossop评分是较低对用Lucemyra治疗患者与安慰剂比较，和在Lucemyra组与安慰剂比较更多患者完成研究的治疗阶段。

来自用Lucemyra治疗最常见副作用包括低血压，心动过缓，嗜睡，镇静和眩晕。Lucemyra 也伴随有一个少数晕厥的病例。Lucemyra影响心脏电活动，它可能增加异常心节律的风险。当Lucemyra被停止，患者可能经受一种明显增加血压。尚未确定在儿童或低于17岁青少年中Lucemyra的安全性和疗效。在一个阶段不使用鸦片类药物后，患者可能是对较低量的鸦片更敏感如复发的确发生，和服用鸦片在量在戒断前曽使用可能导致过量和死亡。 

FDA正在要求15项上市后研究，包括动物和人研究。附加动物安全性研究将被要求支持长期使用(例如在疼痛患者鸦片镇痛药停止中一个逐渐鸦片滴定调整期间)和在儿童中使用。 临床研究将被要求评价Lucemyra的安全性在临床情况其中使用可能被期望超过对产品最大14-天治疗阶段当前地被批准，例如逐渐鸦片滴定调整；收集附加安全性数据对洛非西定[lofexidine]对肝脏的影响；和进一步了解洛非西定被停止后对血压的影响的特征。研究在儿童患者将包括研究的新生与新生儿阿片类戒断综合征和有阿片类戒断综合征相关对停止医学上-处方的鸦片药物不同年龄组儿童研究。

FDA授权这个申请优先审评和快速通道指定，和一个独立FDA咨询委员会支持 Lucemyra的批准在一个会议在3月召开。所为美国卫生和人类服务部五点战略与鸦片危机斗争。the FDA保留承诺鸦片成瘾在所有战线上面对国家危机，有一个显著集中在降低对鸦片暴露和预防新成瘾; 支持有鸦片使用疾患患者；鼓励新颖疼痛治疗的发展和鸦片对滥用和误用更抗性；和采取行动对那些对非法进入和销售鸦片产品贡献对非法采取行动。监管局将还要继续评价如何药物当前地在上市上被使用，在医疗和非法情况两方面；和采取监管行动在需要地方。

FDA授予Lucemyra的批准给予美国WorldMeds LLC公司。

Generic Name: lofexidine
Dosage Form: Tablets
Date of Approval: May 16, 2018
Company: US WorldMeds LLC

Treatment for: Opioid Use Disorder

The U.S. Food and Drug Administration (FDA) has approved Lucemyra (lofexidine), an oral central alpha 2-adrenergic agonist indicated for reducing the severity of withdrawal symptoms in patients experiencing opioid withdrawal.

Read this Patient Information carefully before you start treatment. This information does not take the place of talking with your doctor about your medical condition or your treatment.

Lucemyra can cause serious side effects, including low blood pressure (hypotension), slow heart rate (bradycardia), and fainting.

If you get any of the following signs or symptoms, tell your healthcare provider right away:

· low blood pressure

· slow heartbeat

· dizziness

· lightheadedness

· feeling fainting at rest or when standing up

If you take Lucemyra at home and have any of these signs and symptoms, do not take your next dose until you have talked to your healthcare provider. You should avoid becoming dehydrated or overheated during treatment, which may increase your risk of low blood pressure and fainting. You should also be careful not to stand up too suddenly from lying down or sitting. When your treatment is complete you will need to stop taking Lucemyra gradually or your blood pressure could increase.

For more information about side effects, see Lucemyra side effects.

Increased risk of opioid overdose. After a period of time of not using opioids drugs, you can become more sensitive to the effects of opioids if you start using opioids again. This may increase your risk of overdose and death.

Lucemyra is a non-opioid prescription medicine used in adults to help with the symptoms of opioid withdrawal that may happen when you stop taking an opioid suddenly.

Lucemyra will not completely prevent the symptoms of opioid withdrawal, which may include feeling sick, stomach cramps, muscle spasms or twitching, feeling of cold, heart pounding, muscular tension, aches and pains, yawning, runny eyes and sleep problems (insomnia).

Lucemyra is not a treatment for opioid use disorder. If you have been diagnosed with opioid use disorder (opioid addiction), your healthcare provider may prescribe Lucemyra as part of a complete treatment program for your opioid use disorder (opioid addiction).

It is not known if this medicine is safe and effective in children.

Before you start treatment, tell your healthcare provider about all of your medical conditions, including if you:

· have low blood pressure

· have a slow heart rate

· have any heart problems, including history of heart attack or a condition called long QT syndrome

· have liver or kidney problems

· drink alcohol

· are pregnant or plan to become pregnant. It is not known if Lucemyra can harm your unborn baby.

· are breastfeeding or plan to breastfeed. It is not known if Lucemyra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements, and any medicines you may take for the individual symptoms of opioid withdrawal such as pain relievers or medicines for upset stomach.

Especially tell your healthcare provider if you take benzodiazepines, barbiturates, tranquilizers, or sleeping pills.Taking Lucemyra with these medicines can cause serious side effects. Ask your healthcare provider or pharmacist if you are not sure if you are taking any of these medicines.

· Take this medicine exactly as your healthcare provider tells you to take it.

· Your healthcare provider may change your dose if needed.

· Do not change your dose or stop treatment without talking to your healthcare provider.

· Take the tablets with or without food.

· If you take too much or overdose, go to the nearest hospital emergency room right away.

Do not drive, operate heavy machinery, or perform any other dangerous activities until you know how Lucemyra affects you.

The most common side effects include:

· low blood pressure or symptoms of low blood pressure such as lightheadness

· slow heart rate

· dizziness

· sleepiness

· dry mouth

These are not all the possible side effects. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to US WorldMeds at 1-833-Lucemyra.

· Store at room temperature between 68°F to 77°F (20°C to 25°C).

· Store the tablets in the original container.

· Keep the tablets away from heat and moisture.

· The bottles contain desiccant packs to help keep the tablets dry. Do not remove the desiccant packs until all the tablets are used.

Keep all medicines out of the reach of children and pets.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use this medicine for a condition for which it was not prescribed. Do not give it to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information that is written for health professionals.

Active ingredient: lofexidine

Inactive ingredients: lactose, citric acid, povidone, microcrystalline cellulose, calcium stearate, sodium lauryl sulphate, and Opadry OY-S-9480 (contains indigo carmine and sunset yellow).

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.