Drospirenone-containing combination oral contraceptives include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda and Zarah), Beyaz, and Safyral. For women who choose to use the pill for birth control, in addition to prevention of pregnancy, Yaz and Beyaz have been approved to treat symptoms of premenstrual dysphoric disorder (PMDD) and to treat moderate acne while Beyaz is also approved to raise folate levels.
Though all birth control pills pose a risk of blood clots, there has been concern that birth control pills containing drospirenone have a higher blood clot risk than birth control pills that contain other progestins. Blood clots that form in a deep vein in the body are called deep vein thrombosis (DVT). DVT is a rare birth control pill side effect and could block blood flow. A pulmonary embolism can then occur if a blood clot breaks loose from the vein and moves through the body into the lung. This can lead to death.
Latest News
In June 2011, the U.S. Food and Drug Administration (FDA) chose to inform the public that new information is being investigated as part of the FDA's ongoing safety review of the risk of blood clots with birth control pills that contain the drospirenone. Two recently published studies in the British Medical Journal have investigated whether there is greater risk of deep vein thrombosis and pulmonary embolism in women taking combination pills drospirenone. Both studies found a twofold to threefold greater risk of venous thromboembolic events (blood clots) for women taking birth control pills containing drospirenone as compared to those taking pills containing the progestin levonorgestrel. Because of this recent research, the FDA had decided to further evaluate the risk of blood clots in women who use these products by examining all currently available information as well as the two most recent studies.
UPDATE (April 10, 2012): The FDA released an updated safety announcement explaining that the agency has finished its review of recent observational/epidemiologic research regarding the risk of blood clots in women taking drospirenone-containing birth control pills. Based on this review, the FDA has concluded that pills containing drospirenone may be linked to a higher blood clot risk than other progestin-containing pills. The FDA is also now requiring new labeling for drospirenone-containing pills. The updated labels must include the following information: that some epidemiologic studies have reported as high as a three-fold increase in blood clots risks for these pills when compared to products containing levonorgestrel or some other progestins, whereas other epidemiological studies found no additional risk of blood clots with drospirenone-containing products. Additionally, the revised labels will include a summary of the previously released results of an FDA-funded study of the blood clot risk.
UPDATE (December 7, 2011): The FDA presented a completed full review of the results of its self-funded study, discussing the risks and benefits of drospirenone-containing oral contraceptives at a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. The panel voted 21-5 that current labels of these pills were inadequate and recommended that the FDA require updated labels that specifically explain the potential increased blood clot risk as well stressing that such blood clots could lead to death. The FDA has not yet decided whether it will follow the advisory panel's recommendations. The panel was also almost split (15-11) about the benefits of these pills, with only 58% of the panelists felt the benefits outweighed the risks. 42% of the members felt that the risk was not worth the advantages given that there are alternative combination pill options currently available that could be safer to use.
UPDATE (October 27, 2011): The FDA issued another safety warning stating that the agency is continuing its review of the possible increased blood clot risk with the use of birth control pills that contain drospirenone. The FDA also released its final report of the agency's self-funded research that examined the risk of blood clots in users of several different hormonal birth control methods.
Though the agency has not yet reached a conclusion, it remains concerned, about the potential increased blood clot risk.UPDATE (September 27, 2011): The FDA made a public announcement that it has finished its review of the six conflicting published studies evaluating the risk of blood clots in women using drospirenone birth control pills (this includes the two latest articles published in the British Medical Journal). The FDA explains that there are methodological issues that make the interpretation of the data from these studies complex. Due to that, the FDA has still not reached a formal a conclusion on a woman's blood clots risk. The agency has also begun to receive preliminary data from an FDA-funded epidemiologic study exploring the association of blood clots with several different hormonal contraceptives.
What Does This Mean to Me?
At this point, there is no need to panic if you are currently using a birth control pill that contains drospirenone. The FDA advises that you should not stop taking your pill without first talking to your doctor. If you have any concerns or questions, discuss these with your doctor as well. Additionally, the FDA's 4/10/12 safety announcement advises that you talk to your doctor about your risk for blood clots before deciding which birth control method to use. The FDA is also instructing doctors to consider the risks and benefits of drospirenone-containing birth control pills and a woman's risk for developing a blood clot before prescribing these drugs.
It would also be helpful for you to be able to recognize the symptoms of blood clots. These could include severe chest pain, persistent leg or arm pain (with possible swelling, warmth and redness) or sudden shortness of breath. If you find yourself experiencing any of these symptoms, you should immediately call your doctor.
Also, if you are scheduled for major surgery, you should stop using Yaz, Yasmin, Beyaz or Safyral for at least 4 weeks before the operation and wait 2 weeks afterwards to begin use again. If you use a drospirenone oral contraceptive and are confined to bed rest or a cast, you may have a higher chance of developing a blood clot. Likewise, if you smoke and are over 35 years old, using combination birth control pills greatly increases the risk that you could experience serious cardiovascular events, like blood clots.
The Bottom Line
Overall, if 10,000 women (who are not pregnant and do not use birth control pills) are followed for one year, between 1 and 5 of these women will develop a blood clot. Even though you may be at a greater risk for blood clots if taking a drospirenone birth control pill, I would like to remind you that using any combination oral contraceptive can put you at risk for developing blood clots. The risk of venous thromboembolism, VTE, (deep vein thrombosisand/or pulmonary embolism) in women using any type of combination pill is rare and has been estimated to be 3 to 9 per 10,000 women (per year). This risk is highest during the first year of use (especially during the first 6 months). The greatest risk of VTE seems to be after initially starting a combination pill or restarting the same pill or a different brand (if it has been more than 4 weeks since you last used the pill). You and your doctor should weigh the risks of blood clots (and other side effects) against the benefits of the pill (both for pregnancy prevention and non-contraceptive benefits) -- as pregnancy also increases the risk of venous thromboembolism as much or even more than the use of combination birth control pills (5 to 20 cases per 10,000 women), and this risk increases to 40 to 65 per 10,000 women (per year) who are 12 postpartum.
The FDA offers the following advice:
"To put the risk of developing a blood clot from a birth control pill into perspective: The risk of blood clots is higher when using any birth control pills than not using them, but still remains lower than the risk of developing blood clots in pregnancy and in the postpartum period."
Background
Prior to these newly published studies, previous research on the topic of drospirenone and blood clots have revealed mixed findings.
Two postmarketing studies didn't find any difference in the risk of blood clots between drospirenone-containing products and products containing levonorgestrel or other progestins. However, two other publications in 2009 revealed that the risk of blood clots (VTE) is higher (1.5- to 2-fold higher) in women using drospirenone pills than in women who use pills with levonorgestrel.
The results of these four studies prompted the FDA to require the manufacturers of drospirenone-containing birth control pills to include blood clot risks under the "Warnings and Precautions" section of current prescribing labels. For instance, under the label of Yaz it reads,
"Thromboembolic Disorders and Other Vascular Problems: Stop Yaz if an arterial or venous thrombotic (VTE) event occurs. The use of COCs increases the risk of venous thromboembolism. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years of age), hypertensive women who also smoke.
Epidemiologic studies including a DRSP-containing COC: Several studies have investigated the relative risks of thromboembolism in women using Yasmin compared to those in women using COCs containing other progestins. Two prospective cohort studies, both evaluating the risk of venous and arterial thromboembolism and death, were initiated at the time of Yasmin approval. The first showed the risk of thromboembolism (particularly venous thromboembolism) and death in Yasmin users to be comparable to that of other oral contraceptive preparations, including those containing levonorgestrel. The second prospective cohort study also showed a comparable risk of thromboembolism in Yasmin users compared to users of other COCs, including those containing levonorgestrel. In the second study, COC comparator groups were selected based on their having similar characteristics to those being prescribed Yasmin.
Two additional epidemiological studies, one case-control study and one retrospective cohort study suggested that the risk of venous thromboembolism occurring in Yasmin users was higher than that for users of levonorgestrel-containing COCs and lower than that for users of desogestrel-containing COCs. In the case-control study, however, the number of Yasmin cases was very small (1.2% of all cases) making the risk estimates unreliable. The relative risk for Yasmin users in the retrospective cohort study was greater than that for users of other COC products when considering women who used the products for less than one year. Among women who used the product for 1 to 4 years, the relative risk was similar for users of Yasmin to that for users of other COC products."
