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Questions and Answers – Ongoing safety review of birth control pills containing drospirenone and a possible increased risk of blood clots

On May 31, 2011, the U.S. Food and Drug Administration (FDA) informed the public about new information that is being assessed as part of FDA's ongoing safety review of birth control pills containing the progestin hormone drospirenone. Two recently published studies report that there is an increased risk of deep vein thrombosis (DVT) and pulmonary embolus associated with the use of birth control pills containing drospirenone compared to the risk associated with the use of birth control pills containing a different progestin hormone (levonorgestrel).1, 2

DVT is a rare condition in which blood clots form inside a vein, most commonly in the legs. A blood clot can break loose, move through the body to the lungs, and cause a serious, potentially fatal, problem called a pulmonary embolism (PE).3

The following questions and answers provide an overview of this potential safety issue.

Q1. What is drospirenone?

Q2. Which oral contraceptives contain drospirenone?

Q3. What is a deep vein thrombosis (DVT) and pulmonary embolus (PE)?

Q4. What is already known about combination birth control pills and the risk of venous thromboembolism (VTE)?

Q5. Why is FDA further reviewing the risk of venous thromboembolism (VTE) and birth control pills containing drospirenone?

Q6. How is FDA evaluating these conflicting study results regarding the risk of venous thromboembolism (VTE) in users of oral contraceptives containing drospirenone in order to decide if any regulatory action is needed?

Q7. What should women do if they are currently taking birth control pills containing drospirenone?

Q8. Are there women who should not take birth control pills, particularly those containing drospirenone?

Q9. Has FDA communicated to the public about this issue before?

Q10.What are European regulators doing about birth control pills containing drospirenone?

 

Q1. What is drospirenone?

A. Most birth control pills (combination oral contraceptives) combine a synthetic version of the female hormone progesterone (referred to as a progestin) with a synthetic version of the female hormone estrogen. Drospirenone is one of several different progestins that are used in birth control pills.

 

Q2. Which oral contraceptives contain drospirenone?

Birth control pills containing drospirenone include: Beyaz, Gianvi, Loryna, Ocella, Safyral, Syeda, Yasmin, Yaz, and Zarah.

Some birth control pills containing drospirenone are also approved to treat symptoms of premenstrual dysphoric disorder (PMDD), to treat moderate acne, and to raise folate levels, in women who choose to use an oral contraceptive for contraception.

 

Q3. What is a deep vein thrombosis (DVT) and pulmonary embolus (PE)?

A. Deep vein thrombosis (DVT) is a rare but serious condition where a blood clot forms inside a vein. These blood clots usually form in the lower leg or thigh, but can break loose and travel to other areas of the body such as the lungs. If the clot travels to the lung, it is called a pulmonary embolism (PE), a potentially fatal condition where an artery in the lung becomes blocked.3 DVTs and PEs are also called venous thromboembolic events, or VTEs.

The symptoms of a DVT include the new onset of persistent leg pain, while those of a PE include severe chest pain, and sudden shortness of breath. Women experiencing these symptoms should contact a healthcare professional immediately because VTEs can be life-threatening.

 

Q4. What is already known about combination birth control pills and the risk of venous thromboembolism (VTE)?

A.VTE is already known to be a rare but serious potential side effect of taking any birth control pill containing a progestin and estrogen. The risk of VTE in users of birth control pills is low, although it is higher than the risk of VTE in women who do not take birth control pills. The risk of VTE in pregnant women (about 5 to 20 cases per 10,000 women) 4 is even higher than that in women who take birth control pills.

The drug labels for all combination birth control pills include warning information on the potential risk of VTE and describe additional factors that increase this risk. The risk of VTE associated with birth control pills increases as a woman gets older and is also higher in women who smoke. Usually the risk of VTE is highest during the first year after starting to use a combination birth control pill.

 

Q5. Why is FDA further reviewing the risk of venous thromboembolism (VTE) and birth control pills containing drospirenone?

A. FDA is aware of two newly published studies that evaluated the risk of VTE in women who use birth control pills that contain drospirenone.

The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel.1-2 These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone. This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills.

Conflicting information already exists on this potential increased risk. Two previously published studies, which were conducted at the request of FDA or the European regulatory agencies after drug approval, did not report any difference in risk of VTEs between the drospirenone-containing product and products containing levonorgestrel or other progestins.5, 6 However, two publications in 2009 reported that the risk of VTEs is higher in women using a drospirenone-containing product than in women who use levonorgestrel-containing products. 7, 8 These four earlier studies are already described in the labeling for drospirenone-containing birth control pills.

FDA is currently evaluating all available information to assess fully the VTE risks of drospirenone-containing birth control pills. FDA will continue to communicate any new safety information to the public as it becomes available.

 

Q6. How is FDA evaluating these conflicting study results regarding the risk of venous thromboembolism (VTE) in users of oral contraceptives containing drospirenone in order to decide if any regulatory action is needed?

A. FDA is thoroughly reviewing the two recently published studies, which includes evaluating the strengths and weaknesses of the epidemiologic methods used in these two studies as compared to those used in the other published studies. FDA's overall assessment of VTE risk for drospirenone contraceptives will be based on the strength of the scientific evidence from each of the studies. Data from an additional, large, FDA-funded, study on hormonal contraceptives is also being finalized and reviewed. This study includes over 800,000 US women and is designed to look at thrombotic and thromboembolic risks including VTE in a number of hormonal contraceptive products; results are expected later this summer.

 

Q7. What should women do if they are currently taking birth control pills containing drospirenone?

A. Women taking birth control pills containing drospirenone should continue taking their pills as directed unless told otherwise by their healthcare professional. Women should know how to recognize the symptoms of VTE and should contact their healthcare professional immediately if they experience persistent leg pain, severe chest pain, or sudden shortness of breath. Women should also discuss any questions or concerns about their use of combination birth control pills with their healthcare professional and report any side effects to the FDA MedWatch program using the "Contact Us' information at the bottom of the page.

 

Q8. Are there women who should not take birth control pills, particularly those containing drospirenone?

A. Women with certain conditions or risk factors should not use any combination birth control pill. FDA recommends that women who are over age 35 and smoke should not take any type of combination birth control pill (including those containing drospirenone), due to an increased risk of serious cardiovascular events. The risk of VTE also increases with age and smoking. Women with a history of blood clots, heart attack, or stroke should not take combination birth control pills. Additionally, women who are pregnant or think they may be pregnant should not use combination birth control pills.

Because drospirenone, in contrast to other progestins used in combination oral contraceptives, has the potential to increase serum potassium levels, women with renal or adrenal disease should not use birth control pills containing drospirenone.

For additional labeling information on all combination birth control pills, visit Drugs@FDA.

 

Q9. Has FDA communicated to the public about this issue before?

A. FDA has included warning information about the risk of VTEs in the labels of all combination birth control products. FDA has also communicated previously about the potentially greater risk of VTE with drospirenone-containing birth control products. This prior communication can be found on the Agency's website:

 

Q10. What are European regulators doing about birth control pills containing drospirenone?

A. The European Medicines Agency (EMA) has decided to update the product labeling for oral contraceptives containing drospirenone and ethinyl estradiol regarding the risk of venous thromboembolism after review of all available data, including the same newly published data FDA is reviewing. They have concluded that the risk of VTE for drospirenone-containing birth control pills is higher than that for levonorgestrel-containing pills, but that the risk of VTE with any birth control pill (including those with drospirenone) is very small and that there is no reason for women to stop taking drospirenone-containing birth control pills. 

Because FDA's review of these new data is still ongoing, we are issuing a Drug Safety Communication to alert patients and healthcare providers about this new information that is being assessed as part of our ongoing safety review. Labeling for these products currently describes the previously published studies, which provided conflicting results regarding whether the risk of VTE is higher for women who use birth control pills that contain drospirenone. Upon completion of our review, FDA will provide patients and healthcare providers with appropriate information about VTE risk, including a possible update to labeling, for drospirenone-containing birth control pills.

 

References

1 Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ 2011; 340:d2139.

2 Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ 2011; 340 :d2151.

3 U.S. National Library of Medicine. National Institutes of Health. Health Topics monograph Deep Vein Thrombosis. Available at http://www.nlm.nih.gov/medlineplus/deepveinthrombosis.html Accessed April 28, 2011.

4 James AH. Pregnancy-associated thrombosis. Hematol 2009; 277-85.

5 Seeger JD, Loughlin J, Eng PM, Clifford CR, Cutone J, Walker AM. Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives. Obstet Gynecol 2007; 110(3):587-93.

6 Dinger JC, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007; 75:344-54.

7 Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.

8 Van Hylckama V, Helmerhorst FM, Vandenbroucke JP, Doggen CJM, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339:b2921.

 

 

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