Set to change: Patch, drospirenone OC labels

Focus to be on increased risks

New labeling is being eyed regarding increased risks for blood clots for the contraceptive patch and combined oral contraceptives (COCs) containing the progestin drospirenone (DRSP) following recommendations from joint votes from two Food and Drug Administration (FDA) committees.

The FDA's Reproductive Health Drugs Advisory Committee and the FDA's Drug Safety and Risk Management Advisory Committee Meeting met together on two consecutive days in December 2011 to consider data on drospirenone pills, then the contraceptive patch. At both meetings, the committees evaluated available safety data on both sets of products and voted on the same two questions:

  1. Do you believe that, in the general population of women who desire contraception, the benefits of the [product] for prevention of pregnancy outweigh the risks?
  2. Do you believe the current [product] label adequately reflects the risk/benefit profile for the product?

In voting on whether the current drospirenone labels adequately reflect the risk/benefit profile for these products, 21 of the committee members voted "no," with five voting "yes." The two committees voted 15-11 that the benefits of drospirenone pills outweigh the risks.

In a 20 to 3 vote, with one abstention, the two committees found the current label for Ortho Evra inadequately reflects the risks women face by using it. The two committees voted 19 to 5 that the benefits of the contraceptive patch outweigh the risks.

Recommendations from the advisory committees will be considered by the FDA agency in making its final decisions.

Drospirenone is the progestin contained in the Yaz/Yasmin line of oral contraceptives from Bayer HealthCare Pharmaceuticals of Wayne, NJ, Two other Bayer products also contain drospirenone: Beyaz and Safyral. Drospirenone also is found in generic equivalents: North Wales, PA-based Teva Pharmaceuticals' Ocella and Gianvi; Princeton, NJ-based Sandoz's Loryna and Syeda; and Morristown, NJ-based Watson Pharmaceuticals' Zarah. Watson received FDA approval in November 2011 for Vestura, a generic equivalent to Yaz.

In the Dec. 8 hearing, the committees reviewed all available data regarding use of drospirenone pills, including three studies published in 2011, as well as an FDA-funded study.1-3 "None of the studies to date provides a definitive answer as to the safety of DRSP-containing COCs with regard to the risks of venous thrombotic events [VTE] and arterial thrombotic event [ATE]," states background material prepared by the FDA and presented at the Dec. 8 meeting.4 "The entire body of studies provides conflicting evidence that cannot easily be reconciled by consideration of any single difference among studies."

The FDA in April 2010 approved labeling changes in Yasmin and Yaz to discuss VTE risk in light of two prospective studies5-6 and two epidemiologic studies.7-8 In March 2011, the agency approved a labeling change for Yaz stating that the risk for VTE is greatest in the first six months of use and is present after initially starting a COC or restarting (following a four-week or greater pill-free interval) the same or a different COC.

How should clinicians interpret the data? Keep in mind that retrospective studies that look for rare events have many limitations, says Susan Wysocki, WHNP-BC, FAANP, a Washington, DC-based women's health expert and former president of National Association of Nurse Practitioners in Women's Health. Even though there is an increasing number of studies that have shown a heightened risk of VTE with drospirenone over levonorgestrel OCs, that does not speak to the quality of the studies, she notes.

"We know that events such as VTE tend to occur in the first year of use," says Wysocki. "Therefore, it is particularly important for women who have been doing well on these pills not to panic and stop taking these pills."

According to the chapter on combined oral contraceptives in the newly released 20th revised edition of Contraceptive Technology, "though the relative risk of thrombosis is increased with COC use, most COC users face a low absolute risk of thrombosis because VTE is a rare event in healthy young women."9

Label change for Evra

Since the contraceptive patch (Ortho Evra, Ortho Women's Health & Urology, Raritan, NJ) was approved in 2001, its labeling has been edited to address issues relating to the risk of VTE and exposure to contraceptive hormones seen with Ortho Evra as compared to certain COCs. In March 2011, the boxed warning was edited to include information about the potential risk of VTE and the pharmacokinetics profile of ethinyl estradiol associated with the use of Ortho Evra, which made it more prominent to healthcare providers.

Background material prepared for the Dec. 9, 2011, joint committee meeting offers a similar conclusion as stated in material for DRSP pills.10

"None of the studies to date provides a definitive answer as to the safety of Ortho Evra [patch] with regard to thrombotic and thromboembolic events," the material states. "The entire body of studies provides conflicting evidence that cannot be easily reconciled by considering any single difference among studies."


  1. 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. Doi: 10.1136/bmj.d2151.
  2. Parkin L, Sharples K, Hernandez RK, et al. 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. Doi: 10.1136/bmj.d2139.
  3. Lidegaard ø, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011, Doi: 10.1136/bmj.d6423.
  4. Food and Drug Administration. Center for Drug Evaluation and Research. Background document for joint meeting of Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. Accessed at
  5. Dinger J, Heinemann L, 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; 75:344-354.
  6. Seeger J, Loughlin J, Eng P, et al. Risk of thromboembolism in women taking ethinylestradiol /drospirenone and other oral contraceptives. Obstet Gynecol 2007; 110:587-593.
  7. Lidegaard ø, Løkkegaard E, Svendsen A, et al.. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009. Doi:10.1136/bmj.b2890.
  8. Van Hylckama Vlieg A, Helmerhorst F, Vandenbroucke J, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; doi:10.1136/bmj.b2921.
  9. Nelson AL, Cwiak C. Combined oral contraceptives (COCs). In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
  10. Food and Drug Administration. Center for Drug Evaluation and Research. Background document for joint meeting of Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. Accessed at

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