FDA发布新的药物孕期/哺乳期说明书标准

美国食品和药品管理局（FDA）发布了处方药和生物制剂孕期和哺乳期说明书信息内容和格式的最终标准。

期待已久的PLLR（处方药和生物制剂孕期和哺乳期说明书内容和格式，孕期和哺乳期说明书要求，或孕期和哺乳期说明书标准）是FDA在多方努力下致力于改善处方药说明书内容和格式的其中一部分。PLLR要求说明书上详细描述孕期和哺乳期使用药物的风险和获益来替换现有简单的A、B、C、D、X药品分类，在众多厂家提供药物信息后，PLLR最终完善确认了2008年5月提议中的许多标准。

该标准将于2015年6月30日正式生效。

© Jupiterimages/Thinkstock

据FDA描述，PLLR规定说明书需包括3个小节的具体内容：孕期、哺乳期、对女性和男性生殖系统影响。每个小节的内容中要包括风险概要、数据支持的讨论以及帮助医疗服务者处方和进行咨询决策的相关信息。且如果没有数据可用来指导决策，须加以说明。

孕期小节包括妊娠状态、分娩和产后3个部分，该小节内容将包括孕期的产品使用信息，以及提供孕期女性使用该产品时收集和更新数据的相关登记信息。哺乳期小节替换现有的哺乳母亲小节，将包括母乳喂养期间的产品使用信息，包括药物在母乳中的含量和对幼儿的潜在影响。新增的对女性和男性生殖系统影响部分将描述药品对孕检、避孕和生育的影响。

FDA药物评价和研究中心新药办公室副主任Sandra Kweder医生在新闻发布会上说，现有的A、B、C、D、X分类常被曲解，作为一种药品分类其对药物的风险评定过于简单。使用新的、更为详细说明书识别将更好地描述孕期和哺乳期医生进行处方需要考量的复杂的风险和获益。

“我很激动，因为临床医生在未来可依赖于FDA所批准这部分药物说明便捷地了解到药物更全面的信息以及长期相关性信息——其中有些信息已经消失很多年了，”她同时指出，这些变化特别重要，要知道在美国，每年有超过600万的女性怀孕，且在孕期及哺乳期平均需要服用3~5种不同的处方药物。“我们希望这个新标准可以在医疗保健专业人员和他们的患者在讨论治疗方案时提供帮助，”她说。

重要的是，PLLR确保提供比以往更健全和有效的药物相关数据——并且通过直接与医疗服务人员沟通一直存在的药物相关问题。

除了删除了批准书小节和增加了3个新的小节外，标准化的风险声明因为和批准书一样具有相同的局限性被一同取消了。无意暴露小节因为太过冗长也被删除，同时也因为其暴露风险和有意暴露一致，无需重申。

该标准还规定厂家需要及时更新说明书的最新信息。

旧说明书和新说明书上都包含了药物的大部分信息，但旧说明书上的信息分散且难以查询，因此新的说明书格式要求厂家将药物信息集中在一起保证说明书的一致性，Kweder医生说。现有的药物说明书将逐步以新说明书替换，2015年6月30日后上市的所有药物将直接使用新版说明书。

在一份官方声明中，美国妇产科学学会（ACOG）十分支持“采取必要措施提高使用者对处方药在孕期及哺乳期女性影响的理解”的要求。“FDA对风险和获益信息采用的更新办法将改善所有医生治疗备孕、孕期和哺乳期女性的能力。这也有助于让更多女性了解药物并参与卫生保健的决策，”ACOG声明同时指出，希望处方药和生物制剂说明书的新内容能“增加和参与患者登记一样的临床研究激励方法。”

加州大学儿科教研室临床研究办公室主任、儿科教授Christina Chambers博士在接受采访时赞扬了新的说明书标准，她指出，“这是许多从事孕期和哺乳期女性用药风险和安全咨询顾问们期待已久的最终标准，如Mother To Baby（专业提供畸形信息的专家服务组织）这样服务组织的健康顾问，他们主要为孕期和哺乳期女性提供药物相关信息和暴露风险，同时也参与了最终标准的制定过程。

“Mother To Baby的顾问遍布美国各地，每天为数百名女性解答有关药物暴露问题，他们一直在努力向曲解了药物标签的患者和其他医疗服务者解释不那么有用的A、B、C、D、X分类。新的说明书格式丰富了药物信息和证据，并包括了产妇在治疗（或缺乏治疗）前提下安全性数据的整体情况。这是一个巨大的进步，而且会让我们更加清楚地认识到，了解更多育龄期女性使用的所有药物的孕期数据多么重要，”她说。

Chambers博士是加州Mother To Baby项目主任兼加州大学Mother To Baby研究中心主任。她声明无任何相关利益冲突。

爱思唯尔版权所有  未经授权请勿转载

By: SHARON WORCESTER, Ob.Gyn. News Digital Network

The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.

The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.

The rule will take effect June 30, 2015.

Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.

The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.

The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.

 “I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.

 “It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.

Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.

In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.

The rule also requires that labels be updated as they become outdated.

Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.

In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”

“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”

Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.

 “The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.

Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.