after sulprostone is approximately one in 20,000 cases. So far, myocardial infarction has not been reported as a complication of vaginal gemeprost use, but given the French experience with sulprostone, Roussel-Uclaf recommends that mifepristone plus any prostaglandin not be used in women who smoke more than 10 cigarettes per day, who are older than 35, or who have any other cardiovascular risks (Bygdeman, Appendix B5).

In France, patients must agree to a surgical termination of pregnancy if the medical therapy is not successful. The six children born after unsuccessful therapy with mifepristone are reported to be normal (Ulmann, IOM workshop). However, there is conflicting evidence about the teratogenicity of the mifepristone-prostaglandin regimen (Spitz and Bardin, in press), resulting in the current recommendation of surgical termination in cases of a failed medical procedure.

The ideal combination of an antiprogestin and prostaglandin remains to be established. Certainly, oral administration of prostaglandin may be advantageous for patient convenience. An oral preparation, misoprostol (G.D. Searle & Co., Chicago), is licensed for sale in many countries as a treatment for gastric and duodenal ulcers. Although one patient death was reported during the first trial of mifepristone plus misoprostol (Aubeny and Baulieu, 1991), a much larger study has documented the safety of this protocol. In the latter, 600 mg of mifepristone, plus 400 µg (two tablets) of misoprostol administered 48 hours later, were given to 895 women (Peyron et al., 1993). Approximately 70 percent of women had completely expelled the conceptus four hours after misoprostol ingestion. If expulsion did not occur, a third misoprostol tablet was given. This increased the efficacy to greater than 98 percent. No adverse treatment events were recorded. In addition, uterine cramping or discomfort was reported to be far less than that experienced with injectable or vaginal prostaglandins, with only 16 percent of patients requiring analgesia and 0.1 percent requiring narcotics.

A recent dose-finding study using 200, 400, and 600 mg of mifepristone suggests that doses as low as 200 mg are equally efficacious in inducing first-trimester abortion (Van Look et al., in press). The lowest effective dose of mifepristone in conjunction with prostaglandin is as yet unknown; however, the committee believes that a dose lower than 600 mg is effective.

The cardiovascular side effects in healthy nonsmoking women under the age of 35 appear to be minimal. The additional oral prostaglandin apparently results in a less painful but equally efficacious procedure compared to other prostaglandin preparations, with minimal bleeding and a failure rate of less than 2 percent.

Drug regulatory officials in France, Sweden, and the United Kingdom have judged that the use of antiprogestins in combination with prostaglandin is a safe and efficacious medical treatment for early pregnancy



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