Mifepristone (RU-486) is an antiprogestin that acts to disrupt pregnancy by progesterone receptor blockade. This agent acts on a pregnant uterus by causing necrosis of the decidua with separation of the trophoblast from the decidua, softening the cervix, and increasing uterine contractility and prostaglandin sensitivity. Mifepristone is administered in combination with a prostaglandin, usually misoprostol.

Misoprostol is a prostaglandin E1 analog in pill form that is inexpensive and stable at room temperature. While not approved by the United States Food and Drug Administration for gynecologic care, misoprostol has been well studied for its use as an abortifacient. Misoprostol causes uterine contractions and softens the cervix at any gestational age. Routes of administration vary. Oral and sublingual misoprostol are absorbed rapidly, resulting in higher peak serum levels and higher incidence of gastrointestinal side effects of nausea, vomiting, and diarrhea than the other routes of administration. Vaginal administration results in greater uterine contractility. Recent studies of buccal administration show a pharmacokinetic profile similar to vaginal administration.

Methotrexate is a folic acid antagonist that is cytotoxic to the trophoblast. Methotrexate has been used in combination with misoprostol to induce abortion in pregnancies up to 56 days’ gestational age. It is used less often today due to the greater availability of mifepristone.

The mifepristone-misoprostol regimen was FDA approved in 2000 for medical abortion up to 49 days’ gestational age. This regimen consists of mifepristone 600 mg orally followed 48 hours later by an oral dose of misoprostol 400 μg. The overall complete abortion rate is 92% and is higher with earlier gestations, approximately 96–98% up to 42 days, 91–95% from 43 to 49 days, and less than 85% beyond 49 days. A follow-up examination is performed approximately 14 days after mifepristone administration. If clinical history and physical exam do not confirm expulsion, a transvaginal ultrasound is performed. Uterine aspiration is typically performed if a persistent gestational sac is seen.

Although not FDA approved, evidence has shown that decreasing the mifepristone dose to 200 mg and administering misoprostol 800 μg intravaginally improves complete abortion rates to 95–98% up to 63 days’ gestation, reduces the cost of medical abortion, decreases time to expulsion, and decreases gastrointestinal side effects. Women undergoing medical abortion with these regimens should be offered an antiemetic, as well as sufficient analgesia. These are to be taken before, during or after misoprostol administration or as needed. Investigations have shown that the woman can safely and effectively self-administer the misoprostol in her home 6–72 hours after the mifepristone with similar efficacy. A second dose of vaginal misoprostol may be administered if a gestational sac with or without gestational cardiac activity is present at the follow-up visit approximately 14 days after initiation of treatment. More than half of women with ultrasound evidence of a persistent gestational sac will expel the pregnancy after a second dose of misoprostol. One-third of women with persistent gestational cardiac activity will expel the pregnancy with a second dose, making the second dose of misoprostol a reasonable option.

The methotrexate-misoprostol regimen most commonly utilizes intramuscular administration of methotrexate at the same dose used to treat ectopic pregnancy (50 mg/m2). Overall complete abortion rates are similar to the FDA mifepristone-misoprostol regimen, with 92–96% up to 49 days’ gestation and 82% between 50 and 56 days’ gestation. However, 15–20% of women may wait up to 4 weeks for complete abortion to occur. Oral regimens have been shown to be as effective as intramuscular regimens. Misoprotsol 800 μg is administered 3–7 days after methotrexate by the woman at home. If a gestational sac persists on transvaginal ultrasound approximately 1 week after methotrexate administration, the dose is repeated. If the ultrasound also shows gestational cardiac activity the woman returns in 1 week for follow-up; otherwise, follow-up occurs at 4 weeks after administration of the second dose of methotrexate. If gestational cardiac activity persists 2 weeks after initiating treatment or expulsion has not occurred by 4 weeks after initiation of treatment, uterine aspiration is performed.