Vaginal misoprostol administered at home after mifepristone for abortion - RU486

Journal of Family Practice, April, 1997 by Eric A. Schaff, Lisa S. Stadalius, Steven H. Eisinger, Peter Franks

Mifepristone, better known as RU486, is a synthetic steroid currently used for medical abortion in France, Sweden, United Kingdom, and China. The patent rights were given to the Population Council of New York by the Roussel-Uclaf Company of France to produce the product for American women. European data and a US trial of 2100 women are currently under review by the US Food and Drug Administration (FDA) as part of its approval process. The nonprofit Abortion Rights Mobilization of New York received FDA approval for this trial in May 1996.

Mifepristone acts as a competitive blocker of both progesterone and cortisol by binding to their receptors. Because of its anti-progesterone activity, mifepristone has been developed primarily as a medical abortifacient. Taking a prostaglandin analog 36 to 48 hours after mifepristone to cause uterine contractions increases abortion completion to 96% in pregnancies up to 7 weeks' gestation. (1,2) The prostaglandin currently used in Europe is misoprostol. Misoprostol is an FDA-approved treatment for the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcers.

In Europe, only hospital-affiliated facilities can use mifepristone. The standard treatment is mifepristone 600 mg orally followed 36 to 48 hours later by misoprostol 400 [micro]g administered orally with an observation period of 4 hours in the clinic. The percentage of women experiencing bleeding within 4 hours of taking misoprostol after mifepristone has been reported to be as high as 87%. (3) A review of studies on patient satisfaction of and attitudes toward medical abortion noted two disadvantages: multiple office visits and the waiting time until the abortion was over. (4) Fewer office visits and a shorter interval to abortion completion should improve the acceptability of the procedure.

In a study of 100 women who received oral mifepristone followed by vaginal misoprostol administered in an office setting, complete abortion occurred in 99 women within 4 hours of administering misoprostol. (5) In another study, 270 women, with up to 63 days of amenorrhea, were randomized into two groups to compare oral (400 mg) with vagina (800 mg) administration of misoprostol in an office setting after taking mifepristone. The continued pregnancy rate was 7% with oral administration, compared with 1% for vaginal administration (P=.01). Vaginal administration of misoprostol also caused fewer side effects, leas vomiting (P=.04) and less diarrhea (P=.O02), than oral use. (6) In another study of 1108 women using oral mifepristone and oral misoprostol, an additional dose of misoprostol did not increase the overall efficacy of the procedure, but it did shorten the interval to expulsion. (7) Vaginal misoprostol and repeat doses of misoprostol may improve the effectiveness and shorten the process, thereby increasing the acceptability of this procedure.

While waiting for mifepristone to be approved for use in the United States, the combination of methotrexate and misoprostol has been studied as an alternative medical abortifacient in pregnancies of up to 7 to 8 weeks. (8-10) Methotrexate is alternative to surgery for early unruptured ectopic pregnancies. (11,12) Creinen and colleagues (13) demonstrated that vaginal misoprostol was more effective than oral misoprostol to induce abortion. Self-administration of vaginal misoprostol 6 to 7 days after methotrexate has been found to be sale, effective, and acceptable to women. (10) Although not studied systematically, repeat doses of vaginal misoprostol have been reported to be safe, acceptable, and associated with high effectiveness rates. (10)

The advantages of methotrexate and misoprostol for abortion include the combination's (1) ready availability as "off-label" FDA-approved medications, (2) low cost, (3) few side effects, and (4) effectiveness as a treatment for early ectopic pregnancy. The disadvantages of methotrexate include (1) the concerns inherent in using an anti-metabolite that can affect all dividing cells, and (2) the prolonged waiting interval of up to 2 to 3 weeks to expulsion for up to one third of the subjects. The advantages of mifepristone over methotrexate are its lack of known toxicity and reported short-expulsion interval.

Pending imminent FDA approval of mifepristone, the goals of this study were to determine additional strategies to make the procedures more effective and "user friendly" for US women. In the 48 hours following the administration of mifepristone to women with pregnancies of up to 8 weeks, the study's specific objectives were to determine whether (1) vaginal misoprostol was effective, sale, and acceptable; (2) home administration of misoprostol was sale and acceptable; and (3) an additional dose of misoprostol would shorten the expulsion interval and maintain the procedure's high acceptability by women.

METHODS

The study began in July 1996 after approval from the University of Rochester's Research Subjects Review Board. Women requesting an abortion were enrolled if they fulfilled the following criteria: (1) age 18 years or older, (2) in good health (see Appendix for medical exclusion criteria), (3) a single intrauterine pregnancy of 56 days or less by transvaginal sonogram * (TVS), (4) willing to use mifepristone and misoprostol per protocol, (5) willing to return once 3 to 7 days after mifepristone and, if necessary, on days 15 and 36 until the abortion was complete, (6) access to a telephone and emergency transportation, (7) able to give informed consent, (8) willing to have a surgical (aspiration) abortion if treatment with mifepristone and misoprostol failed, (9) no known allergy to study medications, and (10) residence within 2 hours of study site. The study sponsor, the Abortion Rights Mobilization of New York, supplied the medications. Subjects, or their health insurance, were responsible for the costs of their clinical care ($350).