Bayer's leading oral contraceptives get US label update
This article was originally published in Scrip
Bayer has updated the US label of its leading oral contraceptive pills, Yaz (3mg drospirenone/0.02mg ethinyl estradiol) and Yasmin (3mg drospirenone /0.03mg ethinyl estradiol), to include the results of four studies, including two which showed a comparable risk of thromboembolism with Yasmin compared with older contraceptives.
The update to the US label follows a similar one to the EU label in March; there are no new warnings in either update.
Sales of Bayer's lead pharmaceutical franchise rose by 5% to €1.3 billion last year. Yaz performed particularly strongly in the US and Europe, which offset a decline in sales of Yasmin in the US due to generic competition.
Yaz is the top-selling birth control pill in the US. Both Yaz and Yasmin contain a novel progestin called drospirenone, while Yaz contains a lower dose of oestrogen than Yasmin. Yaz is also approved for the prevention of premenstrual dysphoric disorder (PMDD) and acne in women who also want an oral contraceptive.
However, the franchise has been hit with controversy over its safety, and is facing US lawsuits. Bayer told Scrip: "The complaints we have reviewed so far pertain to side-effects that are warned about in the labelling of all oral contraceptives, including ours. Bayer will defend itself vigorously against these lawsuits."
The labels have always carried a warning that there is a risk of venous thromboembolism (VTE) among all combination oral contraceptives (a class effect), and continue to do so.
"The FDA's thoughtful and balanced analysis will provide helpful information for healthcare professionals to use when they are providing guidance and counsel to patients," said Dr Kemal Malik, chief medical officer at Bayer HealthCare, of the new label update.
The label now details the results of four studies which included Yasmin, but not Yaz, as they were conducted before Yaz was on the market (it received approval in 2006). An ongoing independent study that Bayer is supporting, called INAS, which is due to report next year, is including women on Yaz. However, Dr Leo Plouffe, vice-president of medical affairs women's health at Bayer HealthCare, told Scrip that he does not expect the result to be different from the other two company-sponsored studies given the similarity of Yaz and Yasmin.
Bayer sponsored two independently conducted, large prospective, observational studies (EURAS and INGENIX) in Europe and the US, which were published in 2007. These studies of more than 120,000 oral contraceptive users showed that women taking low-dose oral contraceptives have similar venous thrombotic risk regardless of the progestin used, including the older progestin levonorgestrel.
The label update also includes two other studies which were published last year in the BMJ, which found a higher risk of venous thromboembolism with Yasmin compared with levonorgestrel-containing medicines.
However, with regards to the case-control study (van Hylckama Vlieg et al), the label indicates that the number of VTE cases with Yasmin only made up 1.2% of all cases, "making the risk estimates unreliable".
Concerning the retrospective cohort study (Lidegaard et al), the label indicates that: "The relative risk for Yasmin users in the retrospective cohort study was greater than that for users of other combination oral contraceptives (COCs) when considering women who used the products for less than one year. However, these one-year estimates may not be reliable because the analysis may include women of varying risk levels. Among women who used the product for one to four years, the relative risk was similar for users of Yasmin to that for users of other COCs."
Dr Plouffe said that "variables in the patient population may have driven the risk in the first year". Such variables could include whether women were new users of COCs or not, he said.