Increased Risk of Blood Clots with the Birth Control Patch Ethinyl Estradiol With Norelgestromin (ORTHO EVRA)

The Johnson & Johnson subsidiary Ortho McNeil, announced on Nov. 10, 2005 that the professional product label for one of its products, the birth control patch ethinyl estradiol with norelgestromin (ORTHO EVRA), has been updated to reflect the possibility of an increased risk of potentially fatal blood clots with the use of the patch.  

The written information for patients that must be distributed with each prescription for Ortho Evra will now contain the following information:

Hormones from patches applied to the skin get into the blood stream and are removed from the body differently than hormones from birth control pills taken by mouth. You will be exposed to about 60% more estrogen if you use ORTHO EVRA than if you use a typical birth control pill containing 35 micrograms of estrogen. In general, increased estrogen exposure may increase the risk of side effects. However, it is not known if there are differences in the risk of serious side effects based on the differences between ORTHO EVRA and a birth control pill containing 35 micrograms of estrogen. Talk to your healthcare provider about how this information relates to your use of ORTHO EVRA.

The professional product label, written for pharmacists and doctors, for Ortho Evra will now contain the following bolded warning:

The pharmacokinetic (PK) profile for the ORTHO EVRA patch is different from the PK profile for oral contraceptives in that it has higher steady state concentrations and lower peak concentrations. AUC and average concentration at steady state for ethinyl estradiol (EE) are approximately 60% higher in women using ORTHO EVRA compared with women using an oral contraceptive containing EE 35 mc [micrograms]. In contrast, peak concentrations for EE are approximately 25% lower in women using ORTHO EVRA. Inter-subject variability results in increased exposure to EE in some women using either ORTHO EVRA or oral contraceptives. However, inter-subject variability in women using ORTHO EVRA is higher. In general, increased estrogen exposure may increase the risk of adverse events. However, it is not known whether there are changes in the risk of serious adverse events based on the differences in pharmacokinetic profiles of EE in women using ORTHO EVRA compared with women using oral contraceptives containing 35 mc [micrograms] of EE.

Almost 10 million prescriptions were dispensed for Ortho Evra in the U.S. in 2004.

Ortho Evra was listed as a DO NOT USE drug in the September 2005 Worst Pills, Best Pills News. This warning was based on a July 18, 2005  Associated Press investigative report that linked Ortho Evra to an increased risk of blood clots and deaths (compared to older contraceptives) in some young healthy women.  

The AP used the Freedom of Information Act to obtain adverse drug reaction reports for Ortho Evra from the Food and Drug Administration (FDA). They reported that of the 23 cases in which death was the outcome, physicians reviewing the cases found 17 that appeared to be due to blood clots, including 12 reports in 2004. The FDA estimates that it only receives reports of between one in ten and one in 100 of the serious adverse drug reactions that actually occur.

Ortho Evra was approved by the FDA in November 2001. Unfortunately for the women who have suffered harm this drug, the FDA knew, and was concerned, about an increased risk of blood clots with the use of Ortho Evra, yet the drug was approved. The FDA medical officer responsible for the review of Ortho Evra disagreed with Ortho-McNeil about whether two cases of blood clots in the lungs (pulmonary embolus) in young women participating in the pre-approval clinical trials were caused by the drug. The medical officer wrote:

THE REVIEWER DOES NOT AGREE WITH THE SPONSOR’S [Ortho-McNeil] ABOVE CONCLUSIONS. The two cases of pulmonary embolus, a serious and potentially fatal condition, must be counted as two cases in the ... group [emphasis in the original].

The medical officer also included the following statement in his comments:

The professional product labeling and information written specifically for women using Ortho-Evra should reflect the possible increased risk of venous thromboembolism (VTE) [blood clots] associated with this new transdermal combination hormonal contraceptive containing the new molecular entity progestin norelgestromin (17d-norgestimate).

The complete FDA reviews of Ortho-Evra can be found on the agency’s Web site at: http:// www.fda.gov/cder/foi/nda/2001/021-180_ORTHO.htm.

There is no medically acceptable reason that women should be exposed to a contraceptive product that increases their risk of having a potentially fatal blood clot when there are equally or more effective contraceptives available on the market. The FDA should ask that this drug be removed from the market immediately.

What You Can Do

There is no medical reason for women to use the more dangerous Ortho Evra patch rather than one of the older, better understood, and equally or more effective oral contraceptives.