Media report on Ortho Evra patch sets off safety concerns in women

Patch death rate is triple that expected for the Pill, report claims

Has your office telephone been ringing with questions from patients following a recent media report that the death rate for the transdermal contraceptive (Ortho Evra, Ortho-McNeil Pharmaceutical, Raritan, NJ) is three times that expected for oral contraceptives?

Clinicians already have been fielding questions about the patch’s safety after media reports were issued following the April 2004 death of an 18-year-old woman who had been using the transdermal contraceptive.

The latest media alert springs from an article published by the Associated Press (AP), which contained an analysis of adverse event reports provided by the Food and Drug Administration (FDA). The FDA, responding to a Freedom of Information Act request from the news organization, provided the AP with a database that contained about 16,000 reports of adverse reactions associated with the patch ranging from mild rashes to deaths. According to the AP, 23 deaths associated with the patch were identified; doctors who reviewed the 23 cases found about 17 that appeared to be clot-related, including 12 from 2004, states the news article.1

Lawsuits have since been filed against the manufacturer alleging that the Evra birth control patch is "defectively designed" and "unreasonably dangerous."2

What are the numbers?

The September 2004 media report that sparked initial questions on the patch said it had obtained FDA records, "show[ing] that 17 patch users, ages 17 to 30, suffered fatal heart attacks, blood clots, and possible strokes since August 2002."3

CTU contacted Ortho-McNeil for answers to the following questions:

  1. If 17 patch-related deaths occurred from August 2002 to September 2004, have similar deaths occurred following that time period? If so, how many?
  2. Of the deaths attributed to patch use, how many women had high blood pressure, smoked cigarettes, had a past history of migraine headaches with aura, had a past history of deep vein thrombosis, or were older than age 35?
  3. In the patch-related deaths, can the company break down the figures by where the women were in patch use cycle (week 1, 2, 3, or patch-free)?
  4. How many of the deceased women were younger than age 20? Between ages 21-34? Older than 35?
  5. Can the company provide patch use statistics for 2002, 2003, and 2004?

Michael Beckerich, communications director for Ortho McNeil’s consumer pharmaceuticals & nutritionals group declined to directly address the questions regarding adverse event reports. "In terms of the questions regarding Ortho Evra reports, there have been spontaneous reports of adverse events regarding women and Ortho Evra, but we cannot draw any conclusions on the causal relationship with the medication," he states.

Spontaneous reports are used to monitor products once they are on the market; however, there are some limits to the reliability of spontaneous report information, says Beckerich.

"It is often difficult to determine the relationship of the event to use of a particular product," he states. "It is also difficult to confirm reports when contact information needed to follow up is missing from the report."

More than 5 million women have used Ortho Evra since it was introduced three years ago, reports Beckerich. He provided further information on the method in a statement from Katherine LaGuardia, MD, MPH, director of medical affairs for Ortho Women’s Health, which states in part:

"The mortality rate associated with Ortho Evra use cited in the Associated Press story is misleading because it is based on spontaneous reports and inaccurate citation of clinical data. Spontaneous reports can come from various sources, and there is a significant amount of uncertainty regarding the validity of the information. The AP report states a mortality rate of three in 200,000 from Ortho Evra clinical trials. The data show and the product label reflect there were no fatal events associated with Ortho Evra during clinical trials. We know from industry data that more than 2 million women used Ortho Evra in 2004 compared to the 800,000 women cited in the story."

How to discuss safety?

Is there new information to share with patients about Ortho Evra? Scientific evaluation shows the patch has the same risk as pills for thrombosis.4

Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, offers this observation: There were 17 deaths among women using the patch prior to October 2004. How many have there been since? "We don’t know," he says. "We don’t know the numerator of this problem."

Approximately 5 million women have used Ortho Evra patches since January 2002, Hatcher reports. "We don’t know how many different women in each calendar year used the patch, so we do not know the denominator of this equation," he says. "We simply do not know what 17 deaths mean, nor do we know if the deaths were due to causes possibly related to the patch, such as pulmonary emboli, heart attack, or stroke. I consider it the responsibility of Ortho-McNeil to investigate each death and to come up with answers in the near future to the five questions outlined above."

The patch has been a good method of birth control for many women, and these data do not per se provide any insight as to the relative safety of the patch compared to birth control pills, Hatcher comments.

"One thing these deaths do remind us of is that the same precautions for the prescribing of the patch and the same danger signals for the use of the patch apply as apply to birth control pills," he states. (Teach women to monitor themselves for danger signals by using the "ACHES" mnemonic: abdominal pain, chest pain, headaches that are severe, eye problems, severe leg pain.5)

What are you telling patients in light of the media reports? The National Association of Nurse Practitioners in Women’s Health (NPWH) offers the following talking points:

  • No medication is without risk.
  • Ask women to be honest about their health risks, including smoking, so that their personal risks can be appropriately evaluated.

"For many women, Evra and other hormonal methods of contraception remain safe and are among the most effective ways to prevent unintended pregnancy," states the NPWH.6

References

  1. Mendoza M. Birth-control patch may pose health risk. Washington Post, July 17, 2005. Accessed at: www.washingtonpost.com.
  2. Cable News Network. Women sue birth control patch maker. July 25, 2005. Accessed at: http://money.cnn.com.
  3. Edelman S. Sex patch’ tied to 17 deaths: FDA. New York Post, Sept. 19, 2004. Accessed at: www.nypost.com.
  4. Audet MC, Moreau M, Koltun WD, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs. an oral contraceptive. JAMA 2001; 285:2,347-2,354.
  5. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 18th revised ed. New York City: Ardent Media; 2004.
  6. National Association of Nurse Practitioners in Women’s Health. Ortho Evra media reports sends women looking for answers. Monthly Cycle, August 2005. Accessed at: www.npwh.org.