FDA updates study data information on Ortho Evra contraceptive patch labeling

Earlier data on venous thromboembolism risk supported

The Food and Drug Administration (FDA) has revised labeling on the contraceptive patch (Ortho Evra, Ortho-McNeil-Janssen Pharmaceuticals; Raritan, NJ) to include new epidemiology data on the risks of venous thromboembolism (VTE).

News about the increased risk of VTE is not new. Clinicians have counseled women about such risks since the FDA moved in November 2005 to add an addition to the drug's warning label that the patch exposes women to higher levels of estrogen. In September 2006, the Ortho Evra label reported the results of two epidemiologic studies designed to evaluate the risk of VTE in Ortho Evra users.1,2 One study found that the risk of nonfatal VTE events associated with use of the patch was similar to the risk associated with the use of oral contraceptives (OCs), while the other study showed an approximate twofold increase in the risk of VTE events in patch users compared to OC users.

The new labeling now includes results of a third epidemiologic study, as well as additional information on the risk of VTE in Ortho Evra users from one of the original studies, based on 17 months of data on new cases.3,4 Results from the third study shows an increased risk for VTE among patch users compared to those taking OCs.3

"For women that choose to use contraceptives, it is important that they thoroughly discuss with their health care providers the risks and benefits involved," says Janet Woodcock, MD, the FDA's deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research. "This is an example of FDA working in tandem with the drug manufacturer to keep the public informed of new safety data and epidemiological studies that may impact health decisions about the use of FDA-approved products."

Look at the data

The studies quoted in the Ortho Evra labeling all are epidemiological studies designed to evaluate the risk of developing a serious blood clot in women using the patch compared to women using different commonly prescribed, oral contraceptives containing 30-35 mcg of the estrogen ethinyl estradiol and one of two progestins: norgestimate or levonorgestrel. While the studies were conducted using data from electronic health care claims, they were not structured in exactly the same way, and results of the studies are different, notes the FDA.

The first study, conducted by the Boston Collaborative Drug Surveillance Program, found that the risk of nonfatal VTE events associated with the use of the Ortho Evra contraceptive patch is similar to the risk associated with the use of OCs containing 35 mcg ethinyl estradiol and the progestin norgestimate [OR, 0.9; 95% confidence interval (CI), 0.5-1.6].1 Analysis of 17 months of data on new cases not included in the original report showed a similar finding (OR, 1.1; 95% CI, 0.6-2.1).4

The second study, which included review of patients' charts, was conducted by i3 Ingenix, another group of investigators.2 Results of this study showed an approximately twofold increase in the risk of medically verified VTE events in users of Ortho Evra compared to users of OCs containing 35 mcg estrogen and the progestin norgestimate (OR, 2.4; 95% CI, 1.1-5.5).

The third study, also conducted by BCDSP, compared the risk of nonfatal VTE events among users of Ortho Evra to the risk among users of OCs containing 30 mcg ethinyl estradiol and the progestin levonorgestrel.3 The results showed an approximate twofold increase in the risk of VTE among the Ortho Evra users (OR, 2.0; 95% CI, 0.9-4.1).

Patch use falling off?

Use of the contraceptive patch is experiencing a drop, according to results from CTU's annual Contraception Survey. In 2007, about 84% of survey participants said their facility offered the method, compared to about 88% in 2006. About 93% of participants indicated the method was in use in 2005.

What has led to the decrease? While the product's labeling changes may have affected use for some women, price may be a factor as well. Clinics that no longer qualify for nominal pricing under the federal 340B Drug Pricing Program might not be able to stock the patch, due to increased costs.

A chief benefit of the contraceptive patch lies in its ease of use, because women are no longer tied to taking a daily pill. To use the method, a woman applies a new patch each week for three weeks, with a fourth week being a patch-free week.

Similar convenience is afforded through use of the contraceptive vaginal ring (NuvaRing, Organon USA; Roseland, NJ). To use the method, a woman inserts the ring into the vagina, where it remains for three weeks. The fourth week is ring-free.

While previous studies have directly compared clinical outcomes with use of the patch and combined OCs, as well as the ring and combined pills, the two methods have never been directly compared. Results of a new study that compares use of the patch vs. the ring indicate that women satisfied with combined oral contraceptives and interested in a nondaily method are more likely to continue using the ring than the patch.5

To conduct the study, 500 women who were using OCs were randomized to use the ring or the patch, starting with their next menstrual cycle and continuing for four consecutive menstrual cycles. During the fourth cycle, women returned for a single follow-up visit and evaluation.

For users of the contraceptive ring, rate of completion of three cycles was 94.6% (95% confidence interval [CI], 91-97.1%), compared to 88.2% (95% CI, 83.4-92%) for those assigned to the patch (P = 0.03). Of these women, 71% of ring users (95% CI, 64.8-76.6%) and 26.5% of patch users (95% CI, 21-32.6%) planned to continue their assigned method after study completion (P < 0.001).

Compared with women switching to the ring, those switching to the patch were more likely to experience longer menstrual cycles, increased dysmenorrhea, nausea, mood swings, and skin rash. They were less likely to report frequent vaginal discharge. Ring users required less provider time for telephone consultations compared to patch users.

"These findings do not imply that all women using a combined OC should be counseled to switch to a ring," the study authors conclude. "However, the information from this study can help health care providers counsel women who desire a nondaily combined hormonal contraceptive method."


  1. Jick SS, Kaye JA, Russmann S, et al. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 mcg of ethinyl estradiol. Contraception 2006; 73:223-228.
  2. Cole JA, Norman H, Doherty M, et al. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol 2007; 109(2 Pt 1):339-346.
  3. Boston Collaborative Drug Surveillance Program. Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of EE in relation to nonfatal venous thromboembolism, ischemic stroke and myocardial infarction. Accessed at www.clinicaltrials.gov/ct2/show/NCT00511784.
  4. Jick S, Kaye JA, Li L, et al. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2007; 76:4-7.
  5. Creinin MD, Meyn LA, Borgatta L, et al. Multicenter comparison of the contraceptive ring and patch: A randomized controlled trial. Obstet Gynecol 2008; 111:267-277.