FDA评估紧急避孕药对超重女性的效果

美国食品药品管理局(FDA)启动评估左炔诺孕酮紧急避孕药对超重女性效果不佳的证据，并将决定是否将这一信息添加至药品标签中。

今年11月份，在欧洲销售的Norlevo(含1.5 mg左炔诺孕酮)的说明书中添加了有关体重≥75 kg(165磅)女性效果不佳以及体重>80 kg(176磅)女性无效的警告。虽然Norlevo没有在美国上市，但美国上市的用于年龄≥15岁女性的非处方药Plan B One-Step含有同样剂量的左炔诺孕酮，这类紧急避孕药的标签中没有包含这一信息。


Carolyn Westhoff医生
 
FDA发言人称，针对这一问题，“FDA目前正在对Norlevo标签信息变更所依据的文献及其他现有相关科学信息进行评估，然后将确定是否对已获批紧急避孕药标签进行变更的合理性。” FDA批准Plan B时没有评估体重对有效性的影响。

在一项旨在确定与紧急避孕药失败相关因素的meta分析中，研究者分析了醋酸乌利司他(商品名ella)与左炔诺孕酮紧急避孕药有效性随机对照研究数据。结果显示，对于所有紧急避孕药，肥胖女性受孕风险是正常体重指数(BMI)女性的3倍以上[比值比(OR)，3.06]，而服用左炔诺孕酮肥胖女性受孕风险是服用乌利司他者的4倍(OR，4.41 )。上述分析结果已在2年前发表(Contraception 2011;84;363-7)。

乌利司他属于处方药，事后服用1片。美国专家曾建议，应尽可能选择其他紧急避孕方法。

纽约长老医院/哥伦比亚大学医学中心妇产科学及流行病学教授Carolyn Westhoff医生建议，医生应告知所有体重的女性，含铜IUD是现有紧急避孕措施中最有效的方法。含铜IUD可在月经周期内任何时间植入，具有持续避孕作用。视情况，可在植入时行衣原体常规筛查。

Westhoff医生指出，除含铜IUD外，最有效的紧急避孕药是醋酸乌利司他，生育年龄的女性可在事前开具醋酸乌利司他。“虽然体重较大女性乌利司他有效性有所降低，但并不明显。” 

“据我所知，Plan B似乎应该作为紧急避孕措施中的最后选择。对于没有与医生建立合同关系的女性，这或许是唯一的选择，但对于已经与医生建立合同关系的女性，宜选择其他更有效的措施。” Westhoff医生还是美国计划生育联合会(PPFA)的医学顾问。

PPFA医学标准部主任Karen Shea称，该组织不推荐BMI>30的女性使用Plan B。

PPFA声明指出，Plan B等OTC紧急避孕药，对于BMI≥25的女性可能无效。无论体重如何，3天后OTC药物疗效降低。

事后服用2片的左炔诺孕酮仿制药在美国也有销售。

Westhoff医生声称无相关利益冲突披露。负责在美国销售Plan B One-Step的梯瓦制药公司没有回应置评请求。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

Evidence that the levonorgestrel emergency contraceptive is less effective in overweight women is being reviewed by the Food and Drug Administration, which will determine whether this information should be added to the U.S. labeling of the product.

In November, a warning that Norlevo, which contains 1.5 mg of levonorgestrel, is less effective in women who weigh at least 75 kg (165 pounds) and is not effective in women who weigh more than 80 kg (176 pounds), was added to the label of the product in Europe. No such information is included in the labels of the levonorgestrel emergency contraceptives marketed in the United States. Norlevo, which is not available in the United States, contains the same dose as Plan B One-Step, a 1.5-mg levonorgestrel tablet, available over the counter for women aged 15 years and older in the United States.
 
In response, "the FDA is currently reviewing the available and related scientific information on this issue, including the publication upon which the Norlevo labeling change was based," an FDA spokesperson said. "The agency will then determine what, if any, labelling changes to approved emergency contraceptives are warranted." The FDA’s approval of Plan B did not include a weight-related assessment of efficacy.

The study, a meta-analysis of randomized studies comparing the efficacy of ulipristal acetate (marketed as ella), and levonorgestrel emergency contraceptives, conducted to identify factors associated with failure of the emergency contraceptives, was published more than 2 years ago. For all emergency contraceptives, the risk of pregnancy was more than three times higher (odds ratio, 3.06) among obese women compared with women with a normal body mass index (BMI). But when investigators looked at specific methods, the risk of pregnancy among obese women was four times higher among those who took levonorgestrel (OR, 4.41) compared with those who used ulipristal (Contraception 2011;84;363-7).

Ulipristal is taken as a single tablet and requires a prescription. Experts in the United States already recommend other emergency contraceptive options, when possible.

Ulipristal每次服用1片，属于处方药。此前美国专家已经建议，应选尽可能择其他紧急避孕方法。

Dr. Carolyn Westhoff, professor of obstetrics and gynecology, and of epidemiology, New York–Presbyterian Hospital/Columbia University Medical Center, said she advises clinicians to inform women of any weight that the copper IUD is the most effective form of emergency contraception available. It can be inserted at any time during the cycle, provides ongoing contraceptive protection, and, if indicated, routine screening for chlamydia can be performed at the time of insertion, she pointed out.

After the copper IUD, the most effective emergency contraceptive is ulipristal acetate, which can be prescribed in advance to sexually active women of reproductive age, she added. "While the effectiveness of ella might diminish somewhat with greater weight, that effect is less pronounced," said Dr. Westhoff, who is also the medical adviser to Planned Parenthood Federation of America (PPFA).

"At this point in our understanding, it seems that Plan B should be last choice when providing EC. For women who do not have a relationship to a health care provider, it might be the only choice, but for those women who have a relationship with a clinician, the more effective methods are always preferable," she said.

Planned Parenthood does not recommend Plan B for women with a BMI over 30, according to Karen Shea, director of medical standards at PPFA.

A statement provided by PPFA says that over-the-counter forms of emergency contraception, such as Plan B One-Step, "may not be as effective among women with a BMI of 25 or higher," and points out that "regardless of a woman’s weight, after 3 days, over-the-counter forms diminish in effectiveness."

Generic two-pill formulations of levonorgestrel are also available in the United States.

Dr. Westhoff said she had no relevant financial disclosures. Teva Pharmaceuticals, which markets Plan B One-Step in the United States, did not respond to a request for a comment.