Mifepristone - Indications

Indications

Mifepristone is sold outside the U.S. by Exelgyn Laboratories as Mifegyne, made in France, and is approved for:

1. Medical termination of intrauterine pregnancies of up to 49 days gestation (up to 63 days gestation in Britain and Sweden)
2. Softening and dilatation of the cervix prior to mechanical cervical dilatation for pregnancy termination
3. Use in combination with gemeprost for termination of pregnancies between 13 and 24 weeks gestation
4. Labor induction in fetal death in utero.

Mifepristone is sold in the U.S. by Danco Laboratories as Mifeprex, made in China, and is U.S. Food and Drug Administration-approved to terminate intrauterine pregnancies of up to 49 days gestation. Under the FDA-approved regimen, a 600 mg dose is administered by a clinician following a counseling session. Two days later, a clinician administers 400 µg of another medicine, misoprostol, to induce contractions. In European studies, this method terminated 96 to 99% of pregnancies of up to 49 days gestation, but in one large multicenter trial in the U.S. conducted from September 1994 to September 1995, the efficacy was lower (92%), which the authors of the study suggested may have been due to lack of experience with this method in the U.S. and/or the design of their study. In Europe and China, an observation period of several hours is required after administration of misoprostol. If expulsion of fetal tissue does not occur during the observation period, surgical abortion is offered. There is no required observation period in the U.S., but it is strongly recommended.

According to the current RCOG abortion evidence-based clinical guideline:

• All methods of first-trimester abortion carry a small risk of failure to terminate the pregnancy. The risk for surgical abortion is around 0.23% and for medical abortion between 0.1% and 1.4% (depending on the regimen used and the experience of the centre).
• Medical abortion using mifepristone plus prostaglandin is the most effective method of abortion at gestations of less than 7 weeks.
• Conventional vacuum aspiration below 7 weeks have a higher failure rate than at later gestations. Protocols should include examination of the aspirate for the presence of the gestational sac and/or follow-up serum human chorionic gonadotrophin estimation, to ensure abortion completion.
• Early vacuum aspiration using a rigorous protocol (which includes magnification of aspirated material and indications for serum βhCG follow-up) may be used at gestations below 7 weeks, although data suggest that the failure rate is higher than for medical abortion.
• Medical abortion using mifepristone plus prostaglandin continues to be an appropriate method for women in the 7–9 week gestation band.

Mifepristone can also be used in smaller doses as an emergency contraceptive; if taken after sex but before ovulation, it can prevent ovulation and so prevent pregnancy. In this role, a 10 mg dose is not as effective as the 600 mg dose, but has fewer side-effects. Mifeprex and Mifegyne are only available in 200 mg tablets.

A review of studies in humans found that the contraceptive effects of the 10 mg dose were probably due mainly to its effects on ovulation, and not inhibition of implantation, but "the knowledge of the mechanism of action remains incomplete." Treatment with 200 mg of mifepristone changes steroid receptor expression in the fallopian tube, inhibits endometrial development, and effectively prevents implantation.