Adverse event reports spark discussions on safety of Evra contraceptive patch

Review concerns in counseling on combined hormonal contraception

Did the office telephone lines start buzzing when the media broadcasted reports of adverse events linked to use of the transdermal contraceptive Ortho Evra (Ortho-McNeil Pharmaceutical, Raritan, NJ)? There’s no doubt that clinicians have, since those reports, fielded many questions about the safety of the patch, which has been used by about 4 million women since its November 2001 approval by the Food and Drug Administration (FDA).

Media reports were prompted by the April 2004 death of an 18-year-old New York City woman who had been using the transdermal contraceptive. An autopsy indicated the cause of death was due to a pulmonary embolism, and the medical examiner ruled it a side effect of the birth control device. The New York Post published a report stating that 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."1

The FDA and Ortho-McNeil are examining the adverse event reports; however, both believe that the published numbers may contain duplications, states Kathleen Quinn, agency spokeswoman.

"FDA does not see any safety differences between the patch and pill when it comes to mortality/morbidity," states Quinn. "We will, like with all drugs, continue to monitor the issue and take what action is necessary, if any."

Ortho-McNeil is making the warning information about the risks of Evra use more prominent on its web site, www.orthoevra.com, says Doug Arbesfeld, company spokesman. "Our representatives are talking to providers, reviewing the data with them, and assuring them that we take this very seriously and that we are investigating it," he adds.

Check talking points

The Washington, DC-based Association of Reproductive Health Professionals (ARHP) has issued a set of "talking points" to help clinicians discuss the media reports with their patients. The professional association maintains that "the [New York Post] article is biased and unfortunate, misrepresenting the available data and presenting a skewed picture of adverse events attributable to the contraceptive patch in particular, and medications in general."2

Possible adverse drug reports are submitted voluntarily to FDA by clinicians in the United States and are intended to provide a means to identify rare medical problems that had not been anticipated in the clinical studies undertaken for FDA drug approval, the ARHP publication points out.

"Serious medical events are reported whether or not there is a clear cause-and-effect connection to the drug," states the publication. "For any medication that is widely used, therefore, at least some deaths are bound to occur and be reported."

When talking with patients about use of combined hormonal contraception, which includes oral contraceptives as well as the contraceptive vaginal ring (NuvaRing, Organon, West Orange, NJ), the ARHP advises the following discussion points:

  • Deaths among young women because of medical problems such as heart attack are very rare, and they also are very rare among young women using contraceptive hormones.
  • Taking oral contraceptives or using hormonal contraceptive patches slightly increases the risk of cardiovascular problems — especially for women older than 35 who smoke.
  • The rate for cardiovascular problems estimated for women using the patch is in the range that has been reported for other hormonal contraceptives such as oral contraceptives.
  • Health risks for patch users essentially are the same as risks for women using other hormonal contraceptives.
  • In context, risks for death associated with other common activities such as driving an automobile (1 in 5,900) or continuing a pregnancy to term (1 in 10,000) are significantly higher than risks associated with use of hormonal contraceptives.
  • The risk of death associated with pregnancy — a common outcome among women who don’t use contraception — is far higher than the risk of death associated with using contraceptive pills or the patch. Pregnancy-related deaths, including those at delivery, stillbirth, and ectopic pregnancy, claim the lives of two to three U.S. women every day, with 13 deaths reported for every 100,000 live births in 1999.2

How to explain risks

Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, uses the risk tables published in the latest edition of Contraceptive Technology to help explain the risks of patch use3:

  • If 2 million women become pregnant over a one-year period and carry their pregnancies to term, then one woman out of each 10,000 will die. Of the 2 million women who have become pregnant, 200 will die. If another 2 million women became pregnant the next year, another 200 would die, for a total of 400 deaths in two years.
  • If 200,000 nonsmoking women younger than 35 years of age use pills to prevent pregnancy for one year, then one woman will die. Therefore, if 2 million women use birth control pills for one year, then 10 women will die. If 2 million nonsmoking women use birth control pills for two years, then 20 will die.
  • If 5,300 women who smoke heavily and are younger than 35 years of age use pills for a year, then one will die. If 2 million who smoke heavily and are younger than the age of 35 use birth control pills for two years, then about 750 will die.
  • So the number of deaths for 2 million nonsmoking women who use pills for a year would be about 20; whereas, if they were heavy smokers, the number of deaths would be 750.

"The New York Post article found 17 deaths among 2 million women using the patch over a two-year period," Hatcher observes. "This is clearly far fewer deaths than would have occurred if 2 million women had become pregnant each of two years [400 deaths]."

Seventeen deaths among 2 million patch users over a two-year period is in the range of deaths to be expected if those same 2 million women (most of whom were nonsmokers, but some of whom were heavy smokers) were to have used pills for two years, comments Hatcher.

"The New York Post article underscores the point that deaths and very serious complications may occur from a contraceptive like the patch, but that the risk of death from using the patch is far, far less than the risk of death from pregnancy," he notes.

Talk about ACHES’

The patch, like other forms of combined hormonal contraceptives, carries risks; these risks are spelled out in the product labeling and package insert. The most commonly reported adverse reactions in Evra’s clinical trials included breast symptoms, headache, application-site reactions, nausea and vomiting, dysmenorrhea, and abdominal pain.4,5 In clinical trials, the contraceptive patch was shown to have comparable safety and efficacy with that of oral contraceptives.6

Smoking, hypertension, obesity, and diabetes are risk factors that must be taken into account when prescribing any form of combined oral contraception.7 When providing counseling on combined hormonal contraceptive use, whether patch, pill, or ring, providers should use the "ACHES" mnemonic to teach women potential danger signals:

  • Abdominal pain;
  • Chest pain;
  • Headaches that are severe;
  • Eye problems;
  • Severe leg pain.3

Giving women the information they need to monitor themselves can minimize the risks of any method. The ACHES mnemonic is easy to recall and to teach, says Linda Dominguez, RNC, NP, assistant medical director of the Albuquerque-based Planned Parenthood of New Mexico. The information fits nicely on a small wallet card that can be personalized with the clinic/office contact information as well as individual health information such as current weight, blood pressure reading, or lab values, she advises.

"This minichart information written on the back of the card will be of interest to the patient and will bring her attention back to the ACHES teaching method as well," she states.

References

1. Edelman S. Sex patch’ tied to 17 deaths: FDA. New York Post, Sept. 19, 2004. Accessed at: www.nypost.com/seven/09192004/news/nationalnews/30487.htm.

2. Association of Reproductive Health Professionals. Contraception, the Patch,’ and Reports of Adverse Events Including Death. Washington, DC; September 2004.

3. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 18th revised ed. New York City: Ardent Media; 2004.

4. Smallwood G, Meador ML, Lenihan JP, et al. Efficacy and safety of a transdermal contraceptive system. Obstet Gynecol 2001; 98:799-805.

5. Audet M-C, 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.

6. Burkman RT. The transdermal contraceptive system. Am J Obstet Gynecol 2004; 190(4 Suppl):S49-S53.

7. Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. Am J Obstet Gynecol 2004; 190(4 Suppl):S5-S22.