ST LOUIS (MD Consult) - On September 27, 2010, Bayer HealthCare announced that the US Food and Drug Administration (FDA) has approved Beyaz, an estrogen/progestin combined oral contraceptive that also contains 0.451 mg of levomefolate calcium. Levomefolate calcium is a metabolite of folic acid, a water-soluble B vitamin.

A known association of low folate levels in women and neural tube defects (eg, spina bifida) in their progeny has resulted in recommendations that women of childbearing age supplement their diets with folate, according to a statement by the FDA. The use of Beyaz therefore has the potential to raise folate levels and reduce the risk of neural tube defects in an infant conceived while the mother is taking the product or shortly after she has discontinued use of the product. Folate supplementation is particularly important at least 1 month before and 3 months after conception, according to a press release by Bayer.

The formulation of Beyaz is based on the FDA-approved oral contraceptive Yaz, which contains the same doses of estrogen and progestin. Yaz is approved for the following indications:

·                     prevention of pregnancy;

·                     treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who     choose to use an oral contraceptive for birth control; and

·                     treatment of moderate acne vulgaris in girls and women aged 14 years and older who wish to use an oral contraceptive for pregnancy prevention.

 

The primary efficacy study used to support the approval of Beyaz was a multicenter, double-blind, randomized, controlled US trial in 379 healthy women aged 18 to 40 years. The women were treated with Beyaz or Yaz alone for up to 24 weeks. The use of Beyaz was found to increase folate levels in participants. In women involved in a German study of Beyaz, folate levels remained elevated for several weeks after discontinuation of Beyaz. Safety and efficacy data for contraception, PMDD, and acne indications were obtained from previous Yaz clinical trials.

 

The most common adverse effects reported by users of combined oral contraceptives are irregular uterine bleeding, nausea, breast tenderness, and headaches. Other more serious adverse effects include vascular events and liver disease.

According to a press release by the FDA, the most common adverse events associated with the use of Beyaz are expected to be the same as those for Yaz. No findings from the clinical trials involving Beyaz seem to suggest a change in the overall safety profile compared with that of Yaz.

Beyaz is taken in a 24/4-day regimen consisting of 24 days of 3 mg drospirenone/20 µg ethinyl estradiol with levomefolate calcium 451 µg, followed by 4 days of levomefolate calcium alone. Beyaz is expected to be available in the United States in October 2010.

 

Women who stop taking Beyaz should be advised about maintaining folate supplementation.

圣路易斯(MD Consult)——2010年9月27日，德国拜耳医药保健公司(Bayer HealthCare)宣布，美国食品药品管理局(FDA)已批准Beyaz，即含有0.451 mg  L-5-甲基四氢叶酸钙的雌孕激素复方口服避孕药。L-5-甲基四氢叶酸钙是叶酸(一种水溶性B族维生素)的一个代谢产物。

 

据FDA发表的一则声明，女性叶酸水平较低与其后代发生神经管缺陷(如脊柱裂)有关，故建议育龄期女性在饮食中补充叶酸。育龄女性在服用Beyaz期间或停用此产品后不久，使用Beyaz有升高叶酸水平和降低胎儿神经管缺陷风险的潜在作用。据拜耳公司发表的一篇报道，孕前至少1个月或孕后3个月补充叶酸尤为重要。

 

Beyaz剂型是在经FDA批准的口服避孕药优悦(Yaz)的基础上研发的，含有与优悦相同剂量的雌激素和孕激素。优悦获准的适应证如下：

·                     避孕；

·                     用作选用一种口服避孕药避孕的女性经前烦躁症(PMDD)的对症治疗；

·                     治疗少女和14岁以上(包括14岁)服用口服避孕药避孕的女性中度寻常座疮。

 

美国一项多中心、双盲、随机对照试验在379位18岁~40岁健康女性中对Beyaz的主要疗效进行了研究。受试者分别接受单纯Beyaz或优悦治疗，历时24周。结果发现，Beyaz组受试者的叶酸水平升高。在德国一项关于Beyaz的研究中，受试者停用Beyaz数周后叶酸水平仍维持在升高水平。有关避孕、PMDD和座疮等适应证的安全性和疗效数据来源于先前的优悦临床试验。

 

复方口服避孕药使用者报告的最常见的不良反应有不规则子宫出血、恶心、乳房压痛和头痛。其他较严重的不良反应包括血管事件和肝病。

 

据FDA的一篇新闻，预计使用Beyaz最常见的不良事件与优悦相同。临床试验未发现Beyaz与优悦的总体安全性存在差异。

 

Beyaz的用法为24/4天方案，即3 mg屈螺酮/20 µg乙炔雌二醇和451 µg L-5-甲基四氢叶酸钙服用24天，继之以4天的L-5-甲基四氢叶酸钙单用。预计Beyaz将于2010年10月在美国上市。
建议停用Beyaz的女性继续补充叶酸。