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FDA orders important safety labeling changes for Addyi
FDA命令对“女性伟哥”（Addyi）进行重要的安全标签更改
The U.S. Food and Drug Administration today issued a safety labeling change order to Sprout Pharmaceuticals for their drug, Addyi (flibanserin), that requires the company to revise important safety information that women and their health care professionals need to have when considering use of the drug. The changes are the result of the FDA’s review of postmarketing studies, including one required of Sprout when Addyi was approved in August 2015, to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, as well as other data.
FDA今天发布了一项安全标签变更令，要求公司修改其药品Addyi(氟班色林) 的重要安全信息，这些信息是女性和她们的医疗保健专业人员在考虑使用该药物时需要掌握的。这些变化是FDA审查上市后研究的结果，包括2015年8月批准Addyi治疗绝经前妇女获得性、广泛性性欲减退症(HSDD)时需要的Sprout研究，以及其他数据。
“The FDA helps ensure that the most current safety information about the use of prescription drugs is accurately reflected in product labeling, giving health care professionals and patients confidence that they are able to make the most informed treatment decisions,”said Julie Beitz, M.D. director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research’s Office of New Drugs. “We recognize that women want access to treatments for female sexual dysfunction,and we are committed to helping ensure approved therapies are safe and effective when taken as indicated and to supporting the development of new therapeutic options for female sexual dysfunction.”
“FDA有助于确保最新的安全使用处方药信息准确地反映在产品标签,给卫生保健专业人员和病人的信心并相信他们能够做出最明智的处理决定,”FDA新药评估和研究中心第三药物评估办公室的医学博士Julie Beitz说。“我们认识到女性希望获得对女性性功能障碍的治疗，我们致力于帮助确保批准的治疗方法是安全和有效的，并支持开发新的女性性功能障碍治疗方案。”
At the time of approval, the FDA reviewed data that included several concerning cases of severe hypotension (low blood pressure) and syncope (passing out) when Addyi and alcohol were taken together.As a result, Addyi’s labeling currently includes a boxed warning (the strongest warning the FDA requires), which states that alcohol must be avoided in women treated with Addyi. The FDA also required a risk evaluation and mitigationstrategy (REMS), which requires that health care professionals who prescribe Addyi and pharmacies that dispense Addyi, must be certified with the Addyi REMSprogram and that patients must be counseled about the risk of hypotension and syncope. In addition, the FDA required Sprout to further study the interaction between Addyi and alcohol after approval.
在批准时，FDA审查了包括几个关于Addyi和酒精同时服用时严重低血压(低血压)和晕厥(昏厥)的病例的数据。因此，Addyi的标签目前包括一个框警告(FDA要求的最强烈的警告)，其中规定，接受Addyi治疗的女性必须避免饮酒。FDA还要求制定一项风险评估和缓解策略(REMS)，要求开Addyi处方的卫生保健专业人员和开Addyi处方的药店必须通过Addyi REMS项目的认证，并且必须向患者提供有关低血压和晕厥风险的咨询。此外，FDA要求Sprout在获得批准后进一步研究Addyi与酒精的相互作用。
Based on the results of postmarketing studies, the FDA has determined that changes must be made to Addyi’s labeling to clarify that there is still a concern about consuming alcohol close in time to taking Addyi but that it does not have to be avoided completely.Specifically, the boxed warning, contraindication, warnings and precautions, and adverse reactions sections of labeling are being updated to reflect that women should discontinue drinking alcohol at least two hours before taking Addyi at bedtime or to skip the Addyi dose that evening. Women should not consume alcohol at least until the morning after taking Addyi at bedtime.
根据上市后的研究结果，FDA决定必须对Addyi的标签进行更改，以表明虽然不是完全需要避免，但是在服用Addyi后一段时间内饮酒，依然存在隐患。具体来说，标签上的盒装警告、禁忌症、警告和预防措施以及不良反应部分正在更新，以反映女性应在睡前至少两小时内停止饮酒，或当晚不服用Addyi。女性在睡前服用Addyi后，至少在早上之前不应饮酒。
The FDA is ordering a safety labeling change requiring Sprout to make these changes because the agency was not ableto reach an agreement with the company, which was continuing to request removal of the boxed warning and contraindication about alcohol completely from the product labeling. The FDA determined, based on a careful review of available data that removing this important safety information was not acceptable for the protection of public health.
FDA要求对Sprout的安全标签进行更改，因为该机构未能与该公司达成协议，该公司一直要求将有关酒精的盒装警告和禁药从产品标签上完全移除。FDA根据对现有数据的仔细审查决定，为了保护公众健康，删除这些重要的安全信息是不可接受的。
“We work diligently with companies to make labeling updates but occasionally are unable to reach agreement. In those rare cases, such as with Addyi today, we have important authorities to compel companies to make safety labeling changes that are critical for the safe use ofan approved product. We are taking this action because it is our responsibility to help protect the safety of those who take prescription medicines, which includes helping to ensure that patients are provided access to the most up-to-date information about the drugs they take,” continued Dr. Beitz.
“我们努力与公司合作，更新标签，但有时无法达成一致。在那些罕见的案例中，比如今天的Addyi，我们有重要的权威机构来迫使企业对安全标签做出改变，这对安全使用已获批准的产品至关重要。我们之所以采取这一行动，是因为我们有责任帮助保护那些服用处方药的人的安全，包括帮助确保向患者提供有关他们所服用药物的最新信息。”
The FDA’s decision to order modifications to the warnings about Addyi and alcohol, instead of removing the boxed warning and contraindication completely, is based on two sets of postmarket research studies.
FDA决定对Addyi和酒精的警告进行修订，而不是完全删除盒装警告和禁忌症，这是基于两组上市后研究得出的结论。
In the FDA required postmarket in women who took Addyi and drank alcohol at the same time, there were missingor delayed measurements for blood pressure from when the women were first laying down towhen they stood up that are critical in determining the risk of hypotension and syncope when taking Addyi and alcohol together. The FDA’s specific concerns with the trial included:
应FDA的在对同时摄入Addyi和酒精的女性进行FDA指定的测试过程中，对女性血压监测数据的收集存在缺失或数据采集延迟的问题，受试女性从躺下到重新站立起来的这个时间段的血压数据对确定服用Addyi和酒精时低血压和晕厥的风险至关重要。
While there were no reports of syncope orhypotension needing intervention amongst women in the trial, the safety precautions built into this trial did not allow for an adequate assessment of this risk. For example, women with low blood pressure while lying down or with symptoms that could be related to low blood pressure (such as dizziness) were not permitted to stand up to have blood pressure measurements taken or had to have repeated blood pressure measurements while lying down until they were high enough for the women to safely stand up. As a result, the data collected had missing or delayed blood pressure measurements from these women while standing.
虽然在试验中没有报告显示妇女晕厥或低血压需要干预措施，但纳入该试验的安全预防措施并不能充分评估这一风险。例如, 当患有低血压的女性躺着或产生低血压相似症状时(如头晕) 是不允许站起来测血压或不得不在躺着的时候重复测量血压,直到血压值恢复到他们能够安全的站起来。作为结果来说，对女性站立血压监测数据的收集存在缺失或数据采集延迟的问题。
Many more women had missing or delayed blood pressure measurements when they took Addyi and alcohol together compared to when they received alcohol alone or Addyi alone.
与单独饮酒或者单独服用Addyi的女性相比，更多的女性在同时服用Addyi和饮酒时错过或推迟了血压测量。
The amount of missing blood pressure measurements peaked around the time when Addyi’s blood levels were highest in those taking Addyi with alcohol.
当Addyi的血浓度在那些同时服药和饮酒的女性中达到最高的时候，血压测量的缺失也在那时候到达了巅峰。
The pattern of the missing or delayed measurements provides further evidence of an interaction between Addyi and alcohol that can increase the risk of hypotension and syncope. Given these results, the FDA has determined that the boxed warning and contraindication continue to be warranted. Women at home will not have the safety measures that were included in this trial or necessarily have access to immediate assistance if they were to experience severe hypotension or syncope, which can lead to serious outcomes including falls, accidents and bodily harm.
缺失或延迟测量的模式为Addyi和酒精之间的相互作用提供了进一步的证据，这种相互作用会增加低血压和晕厥的风险。鉴于这些结果，FDA已决定，框警告和禁忌症的标注仍是必要的。在家的妇女将不具备本试验所包括的安全措施，如果她们发生严重低血压或晕厥，也不一定能获得立即援助，而这些情况可能导致严重后果，包括跌倒、事故和身体伤害。
In other postmarketing trials, results showed that the risk of severe hypotension and syncope was reduced when women who consumed up to two alcoholic drinks waited at least two hours before taking Addyi. The FDA has found these results sufficient to support a modification tothe boxed warning and contraindication stating that Addyi and alcohol must notbe taken close in time (i.e. not within two hours).
在其他上市后的试验中，结果显示，当女性在服用Addyi前至少要等两个小时，才饮用两种酒精饮料时，患严重低血压和晕厥的风险就会降低。FDA发现，这些结果足以支持修改方框警告和禁药说明，Addyi和酒精不能在近距离服用(即不能在两小时内)。
Addyi is a serotonin 1A receptor agonistand a serotonin 2A receptor antagonist, but the mechanism by which the drug improves sexual desire and related distress is not known. Addyi is taken once daily. It is dosed at bedtime to help decrease the risk of adverse events occurring due to possible hypotension, syncope and central nervous system depression (such as sleepiness and sedation). Patients should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress. The most common adverse reactions associated with the use of Addyi are dizziness, somnolence (sleepiness), nausea, fatigue, insomnia and dry mouth.
Addyi是一种血清素1A受体激动剂和血清素2A受体拮抗剂，但该药物改善性欲和相关痛苦的机制尚不清楚。Addyi每天服用一次。睡前服用该药有助于降低因可能的低血压、晕厥和中枢神经系统抑郁(如嗜睡和镇静)而发生不良事件的风险。如果患者没有报告性欲和相关痛苦的改善，那么他们应该在8周后停止治疗。使用Addyi最常见的不良反应是头晕、嗜睡、恶心、疲劳、失眠和口干。
The Food and Drug Administration Amendments Act of 2007 gave the FDA the authority to require and, when necessary, order safety labeling changes to reflect new safety information about an approved prescription drug. Failure to respond to the order as outlined may result in monetary fines and additional enforcement actions including seizure of the product and injunction. Sprout has until April 16,2019, to appeal the order through the FDA’s formal dispute resolution process.
2007年美国食品和药物管理局修正案授予FDA权力，要求并在必要时命令更改安全标签，以反映有关已批准处方药的新安全信息。未能按照规定对命令作出反应，可能会导致罚款和包括没收产品和禁令在内的额外执法行动。Sprout可以在2019年4月16日前通过FDA的正式争端解决程序对该命令提出上诉。
The FDA, an agency within the U.S.Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccinesand other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply,cosmetics, dietary supplements, products that give off electronic radiation,and for regulating tobacco products.
FDA是美国卫生和公众服务部的一个机构，它通过确保人类和兽药、疫苗和其他供人类使用的生物制品以及医疗器械的安全性、有效性和安全性来保护公众健康。该机构还负责我国食品供应、化妆品、膳食补充剂、散发电子辐射的产品的安全和保障，并负责监管烟草产品。
本文内容取自 FDA
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