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Transdermal systems may boost compliance, lower unintended pregnant
Think about your patients who have problems remembering to take their daily birth control pill, and images of the forgetful teen, the busy mother, and the pressed-for-time working woman immediately come to mind. What if a transdermal contraceptive patch could provide them with safe, effective birth control, thus eliminating the need for a daily pill?
Several such patches are now in the research pipeline. While their safety and efficacy profiles are yet to be fully established in large-scale trials, contraceptive transdermal systems represent yet another potential option with a built-in convenience factor.
Interest in contraceptive patches was heightened this summer when news broke about Evra, a transdermal system under development by Ortho-McNeil Pharmaceuticals of Raritan, NJ. Preliminary information on Evra and other products under development was reviewed during a meeting of financial analysts hosted by Johnson & Johnson of New Brunswick, NJ, the parent company of Ortho-McNeil.
Company comments about Evra are limited because the company has yet to submit regulatory filings on the product, says Linda Fedow, director of public affairs for Ortho-McNeil. The company is in Phase III clinical trials, but Fedow declines to discuss its findings.
"What I can tell you is that we believe that this product is highly innovative, and its contraceptive efficacy is comparable to the most popular and some of the best oral contraceptives," she says. "Other than that, we really can’t speak to [risks and benefits] because it is so early."
Evra will contain the estrogen ethinyl estradiol and an active metabolite of norgestimate, which family planners will recognize as the progestin used in Ortho-Cyclen and Ortho Tri-Cyclen, two of the company’s most popular oral contraceptive brands. The technology for the transdermal system is being supplied by outside partner Cygnus, a company in Redwood City, CA, that focuses on the development and manufacture of diagnostic and drug delivery systems.
The patch is being developed so it can be used on any one of four areas of a woman’s body: the abdomen, the buttocks, the upper outer arm, and the upper torso, Fedow reports.
"We believe this will be a very novel system for women," she says. "We believe it does have a convenience factor and that it will adhere well to a woman’s skin, allowing her to perform all different types of routine daily activities, whether it be bathing, swimming, or exercise."
Women are looking for long-term birth control methods that offer the efficacy of the Pill but are easily reversible, says Fedow. Evra is squarely aimed at those potential users.
The Population Council in New York City also is researching a contraceptive patch, confirms Sandra Waldman, director of public information. The transdermal system uses Nestorone, a progestin developed by the council. [Contraceptive Technology Update reviewed the council’s partnership with Miramar, FL-based Sano Corp. in developing transdermal patches for both contraception and hormone replacement therapy (HRT) in its October 1997 issue, p. 121. Under a December 1997 stock acquisition by Elan Corp. in Dublin, Ireland, Sano now operates as a business unit of Elan Pharmaceutical Technologies, Elan’s drug delivery division.1] "The Population Council is looking at patches that potentially can be used for contraception, including emergency contraception, and hormone replacement therapy," reports Waldman. "The primary hormone we are using is Nestorone, a versatile progestin that is readily absorbed through the skin into the bloodstream."
The council’s work is in a preliminary stage, she notes. Scientists also are looking at use of Nestorone for use in contraceptive vaginal rings. One version of such a ring contains a combination of the estrogen ethinyl estradiol and Nestorone, while the other contains Nestorone alone. (For more information on those research developments, see CTU, May 1998, p. 57.)
HRT patches on market
While the Evra patch may be the first contraceptive transdermal system to come under federal Food and Drug Administration (FDA) review, it won’t be the first patch developed specifically for women. American women already are becoming familiar with transdermal technology with the advent of systems used to deliver HRT.
There are at least six estradiol patches now on the U.S. market:
• Alora from Proctor & Gamble Pharmaceu ticals of Cincinnati;
• Climara from Berlex Laboratories of Wayne, NJ;
• Esclim from Groupe Fournier of Dijon, France;
• Estraderm and Vivelle, both of Novartis Pharmaceuticals Corp. of East Hanover, NJ;
• FemPatch from Parke-Davis of Morris Plains, NJ.
CombiPatch received FDA approval in August 1998 as the first U.S.-approved HRT patch to combine estrogen and progestin. The system, which delivers the estrogen 17-beta-estradiol and the progestin norethindrone acetate, is marketed by Rhône-Poulenc Rorer of Collegeville, PA.
By delivering a steady flow of drugs over an extended period of time, transdermal patches avoid the "peak and valley" hormone effect of pills or injections, thereby reducing associated side effects.2
"The advantage of the transdermal system is the consistent blood levels," observes David Archer, MD, professor of obstetrics and gyne cology at the Jones Institute for Reproductive Medicine in the Eastern Virginia Medical School in Norfolk. "The rapid absorption and high blood levels with oral administration are felt to be the cause of nausea [sometimes associated with pill use]; transdermals may reduce this effect."
While there is no comparable contraceptive patch yet on the market, research comparing women’s experiences with HRT patches vs. pills shows mixed acceptance of transdermal technology. In one 1997 presentation, researchers reported that more women seem to prefer transdermal therapy to oral HRT, because transdermal therapy ensures more constant estradiol levels.3 However, a study published in 1998 indicated that among women starting HRT, those using a semiweekly transdermal estradiol regimen have a lower rate of continuation than do those using daily oral estrogen therapy.4
"Transdermal HRT systems have not found large acceptance from the consumer," Archer says. "I believe it is due to local [skin] irritation and lack of a good adhesive."
Users must remember to change transdermal patches once or twice a week, which differs from daily dosing, he notes. This may be seen as a benefit by a large part of the population. Contraceptive patches may be embraced by those women who want to try something new, Archer says. By developing a stylish backing for a contraceptive patch, marketers may tie into the recent increase in interest in tattoos and body art, he suggests.
The true test of contraceptive transdermal patches will be the release of full safety and efficacy data. If the patches don’t provide effective birth control or are linked to unacceptable side effects, they will not be accepted by women.
"No data on bleeding or other related issues that can influence compliance is yet available," Archer says. "This information will be needed to determine utilization."
1. Elan Corp. and Sano Corp. Elan to acquire Sano Corp. in an all-stock transaction. Press release. Dublin, Ireland and Miramar, FL: Dec. 15, 1997.
2. Associated Press. J & J developing new contraceptive. New York, NY: July 21, 1999.
3. Bailey J. Symposium report: New trends in transdermal HRT and aspects of climacteric psychology. Eur Menopause J 1997; 4:I-IV.
4. Ettinger B, Pressman A, Bradley C. Comparison of continuation of postmenopausal hormone replacement therapy: Transdermal versus oral estrogen. Menopause 1998; 5:152-156.