FDA更改所有缓释/长效阿片类药品说明书

美国食品药品理局（FDA）宣布将更改治疗慢性疼痛的所有缓释及长效阿片类止痛药的说明书。另外，从现在起将要求药品生产商进行上市后研究，以帮助FDA确定是否有必要采取进一步措施。

“FDA下令要求更改安全说明书和进行上市后研究，以抵制这些强效药的误用、滥用、成瘾、过量使用和致死，这已经伤害了太多患者，破坏了太多家庭和社团，”FDA局长Margaret A. Hamburg在9月10号的记者会上说道。“今天的举措显示FDA决心降低长效和缓释阿片类药品的严重风险，同时尽力为依赖这些药物镇痛的患者保留获取这些药品的正当渠道。”

缓释及长效阿片类药品包括氢吗啡酮、吗啡、氧可酮、氧吗啡酮和他喷他多。对说明书的变更将包括剂量、用法、警告和注意事项、药物相互作用、特定人群用法、患者咨询信息和用药指导。对缓释/长效阿片类止痛药的风险评估与减轻策略（REMS）也将做相应修改，以反映最新信息。

FDA药品评价与研究中心审批管理办公室副主任Douglas Throckmorton认为，这项关键变更的重心是让处方医生不再仅依据疼痛等级来评估患者疼痛，而是依据一种更加“全面的评估方法”。“更新后的适应证规定缓释、长效阿片类药品适用于严重到只能每天、24小时连续、长期使用阿片类药品处置而其他替代方法无效的疼痛，”在记者会前发布的FDA声明中记录的替代镇痛用药包括速释类阿片类药品，此药品目前不受该说明书变更规定的影响。

Throckmorton医生说他希望FDA的这项措施是“鼓励人们思考如何充分使用这类药品所做的更广泛的努力”的一部分。在被问到处方医生和他们的患者是否尚未解决使用这些阿片类药品（目前这些药品说明书上规定用于发生“中、重度疼痛”而非“持续性”疼痛的患者）伴随的风险和收益时，Throckmorton医生说这些说明书变更“将有助于凸显在繁忙的临床实践中进行交谈的重要性”。

FDA公告的发布背景是医学文献中关于阿片类药品使用的内在风险的数据不断增多，以及FDA归档了两份要求改变阿片类药品处方方式的公民请愿书，其中之一是由“负责任地开具阿片类药品处方”提交的。有关阿片类药品使用的一个关注点是FDA药品安全与风险管理咨询委员会在1月份以19:10表决通过将氢可酮联合用药从《违禁物质法》（Controlled Substances Act ，CSA）规定的Ⅲ类目录调整到Ⅱ类目录。促成此次表决的是美国缉毒局向FDA发出的对用药过量、冒用和滥用做出反应的呼吁。FDA官方在记者会上援引的统计数据中包括了2009年发生在美国的近16,000起与阿片类药品有关的死亡案例。

在谈到用药剂量和疗程的重要性时，Throckmorton医生说FDA目前没有足够的信息来改变这些药品的处方方式，但是临床试验等上市后研究和其他为期12周及以上的研究可能有助于提供这方面数据。“我们希望部分研究能在2年后为我们提供信息。这样，到2015年底，我们将掌握更多。”

FDA在记者会上还宣布将对缓释/长效阿片类止痛药增加一个黑框警告，用来警示准妈妈注意新生儿阿片类药品戒断综合征（NOWS），这种病症可能危及生命，需要根据新生儿科专家制订的方案进行诊疗。新生儿如果在出生前于母体内接触了阿片类药品，就能发生NOWS。症状可能包括难以喂养、呼吸急促、发抖和啼哭过多或哭声尖锐。

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By: WHITNEY MCKNIGHT, Internal Medicine News Digital Network

The U.S. Food and Drug Administration has announced that it is making classwide label changes to extended-release and long-acting opioid analgesics for treatment of chronic pain. In addition, drug manufacturers will now be required to conduct postmarket studies to help the agency determine whether further actions are merited.

"The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities," Dr. Margaret A. Hamburg, FDA commissioner, said Sept. 10 in a press briefing. "Today’s action demonstrates the FDA’s resolve to reduce the serious risks of long-acting and extended release opioids while still seeking to preserve appropriate access for those patients who rely on these medications to manage their pain."

Extended-release and long-acting opioids include hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol. Changes to labels will include updated information about dosage and administration, warnings and precautions, drug interactions, use in specific populations, patient counseling information, and the medication guide. Modifications also will be made to the extended-release/long-acting opioid analgesics Risk Evaluation and Mitigation Strategy (REMS), to reflect the updated information.

The key change centers on moving prescribers away from the assessment of a patient’s pain based solely on a pain scale to a more "comprehensive one," according to Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research. "The updated indication states that extended-release, long-acting opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate," Dr. Throckmorton stated in the briefing. Alternative pain medications noted in an agency statement released prior to the briefing include immediate-release opioids, which are currently unaffected by the agency’s labeling changes.

Dr. Throckmorton said he hopes the FDA’s action is part of a "broader effort to encourage people to consider how best to use these medications." When asked whether prescribers and their patients weren’t already addressing the risks and benefits involved in the use of these opioids, the current labeling for which indicates their use in patients experiencing "moderate to severe pain," rather than "round-the-clock" pain, Dr. Throckmorton said the labeling changes "will help reinforce the importance of the conversation in a busy practice."

The agency’s announcement comes amid growing data about the inherent risks of opioid use reported in the medical literature and the filing with the FDA of two citizen petitions to change how opioids are prescribed, including one by the Physicians for Responsible Opioid Prescribing. Also part of the focus on opioid use is the 19 to 10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January to reschedule hydrocodone drug combinations from schedule III under the Controlled Substances Act (CSA) to schedule II. The vote was prompted by the U.S. Drug Enforcement Administration’s call for the FDA to react to evidence that the medications are overprescribed, diverted, and abused. Statistics cited by FDA officials in the briefing included nearly 16,000 opioid-related deaths in the United States in 2009, reflecting a 300% increase in the last 20 years.

Speaking about the importance of the dosage and duration of the medications, Dr. Throckmorton said the agency did not have enough information at this time to make changes to how these drugs are prescribed, but that the postmarket studies such as clinical trials, and other studies of at least 12 weeks’ duration, would play a role in providing this data. "We expect some of those studies will provide information for us to use in 2 years. So, by end of 2015, we will have more," Dr. Throckmorton said.

Also announced in the briefing was the addition of a boxed warning on extended-release/long-acting opioid analgesics to warn expectant mothers of neonatal opioid withdrawal syndrome (NOWS), which might be life-threatening and require management according to protocols developed by neonatology experts. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.