FDA寻求更安全的阿片类使用策略

美国食品药品管理局(FDA)近日批准对缓释和长效阿片类药物实行风险评估和降低策略(REMS)。

FDA局长Margaret A. Hamburg博士在新闻发布会上称，在确保中重度持续性疼痛患者能够继续获得高效镇痛药物的同时，作为遏制这类处方药日益膨胀的滥用、误用和过量使用趋势的重要环节，采取上述措施早在预料之中。

Hamburg博士指出，这项涉及约30种上市药品的新安全措施，要求药品制造商向开发和提供培训的继续教育机构提供基金，保证在2013年3月1日之前向处方医生提供FDA批准的培训资料。此外，REMS还包括向处方医生发放有关药物安全和有效性的患者咨询手册、及时更新的单页患者用药指南、实施计划以及有关该计划对药物安全使用影响的定期评估报告。FDA将根据评估报告在必要时对该计划进行调整。

据FDA药物评价和研究中心新药办公室主任John Jenkins博士介绍，之所以关注缓释和长效阿片类药物，是因为这些药物存在亟待认真解决的特殊安全性问题。包括氢吗啡酮、羟考酮、吗啡、羟吗啡酮、美沙酮、芬太尼透皮贴剂以及丁丙诺啡透皮贴剂在内的这些药物，即便处方合理也可能出现问题。

Jenkins博士指出，REMS中涉及处方医生教育的内容包括个体患者阿片类治疗风险与受益、合理选择患者、患者管理与监测以及患者咨询等信息，以及潜在滥用、误用和过量使用及其证据确认指南等。及时更新的用药指南和患者咨询文件包括如何安全使用、储藏和发放这类镇痛药物的信息，确认潜在过量使用迹象明确指南以及预防家庭成员和来访者意外暴露的建议等。

Hamburg博士称，针对该计划内容的评估和核查，FDA已经制定了期望制造商能够达到的相关目标，包括处方医生完成培训的比例以及处方医生对风险信息了解的评估。但她声称，并非强制要求处方医生参与教育项目。此外，评估内容还要求评价REMS是否对患者获得这些药物产生不利影响。她强调，“必须保证疼痛患者在需要时能够继续得到这些药物。”

新的REMS计划是白宫在2011年为解决处方药滥用问题而发布的多部门协作的国家战略的一部分。Hamburg博士称，处方药滥用是美国发展最迅猛的药物问题，尤其是阿片类过量使用，2008年导致大约15,000名美国人死亡，2009年则增加至近16,000人。这项名为“流行病：应对美国处方药滥用危机”的国家计划建议扩大以州为基础的处方药监测方案，探索方便、环保的未使用药物处置推荐规范，并呼吁采取立法措施减少“逛医生(指某些患者频繁更换医生的现象)”和“药片作坊”。

在缺少立法改变的情况下，则需要执行综合性白宫计划，而REMS“是FDA实施的一项补充处方医生培训和消费者信息的重要且及时的步骤，”白宫国家药品控制政策办公室主任R. Gil Kerlikowske说道。

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By: DIANA MAHONEY, Internal Medicine News Digital Network
A risk evaluation and mitigation strategy for extended-release and long-acting opioid medications has received Food and Drug Administration approval.

The move has been anticipated as an important element in an attempt to stem the swelling tide of abuse, misuse, and overdose of these prescription drugs while assuring continued access to the highly potent analgesics for patients with moderate to severe persistent pain, Dr. Margaret A. Hamburg said in a media briefing today.

The new safety measures, which pertain to approximately 30 currently available medications, will require the manufacturers of the drugs to make FDA-approved education materials available to prescribers no later than March 1, 2013, via development grants to continuing education providers who will develop and deliver the training, said Dr. Hamburg, commissioner of the FDA. In addition, the risk evaluation and mitigation strategy (REMS) will include the distribution of a patient counseling leaflet to prescribers regarding the safe and effective use of the drugs; an updated, single-page medication guide for consumers, an implementation plan, and periodic assessments to evaluate the impact of the program on the safe use of these products, which the FDA will review and use to tweak the program as needed, she said.

"It is important to note that we are focusing on extended-release and long-acting opioid medications ... because these have very specific safety problems that have to be addressed very carefully," according to Dr. John Jenkins, director of the Office of New Drugs within the FDA’s Center for Drug Evaluation and Research. These drugs, including hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl, and transdermal buprenorphine, "can cause problems even when prescribed appropriately."

The prescriber education component of the REMS will include information regarding the risks and benefits of opioid therapy for individual patients, choosing patients appropriately, patient management and monitoring, and patient counseling, Dr. Jenkins explained. It will also include guidance on the potential for misuse, abuse, and addition, as well as recognizing evidence for these outcomes. The updated medication guide and patient counseling document will include information on how to safely use, store, and dispose of these analgesics, specific instructions for recognizing the signs of potential overdose and advice for preventing accidental exposure to family and household visitors, he said.

With respect to the assessment and auditing component of the program, the FDA has established goals, which the manufacturers are expected to achieve, for the percentage of prescribers who complete the training and for assessing prescribers’ understanding of the risk information. Participation in the educational programs is not mandatory for prescribers, Dr. Hamburg stated. The assessments are also required to evaluate whether the [REMS] adversely affect patient access to these drugs, she said. "Patients in pain must have continued assess to medications they need," she added.

The new REMS program is one component of a multiagency, national strategy unveiled by the White House in 2011 to address prescription drug abuse, "which is this country’s fastest-growing drug problem," said Dr. Hamburg, noting that opioid overdoses in particular were the cause of approximately 15,000 deaths among Americans in 2008 and nearly 16,000 in 2009. Called Epidemic: Responding to America's Prescription Drug Abuse Crisis, the national plan suggests expansion of state-based prescription drug-monitoring programs; seeks creation of recommendations for convenient and environmentally responsible ways to dispose of unused medications; and calls for legislative action to reduce "doctor shopping" and "pill mills."

In the absence of the legislative changes needed to fulfill the comprehensive White House plan, the REMS "is an important and timely step by FDA to supplement prescriber training and consumer information," R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy, said during the telebriefing.