Mifepristone

F An antagonist that blocks progesterone, a hormone essential to pregnancy, and along with another medication misprostol enables the body to terminate pregnancy.

Approved for use up to 70 days into a pregnancy

Mifepristone, also known as RU-486.

Adverse effects are mild: cramping or abdominal pain.

A medication typically used in combination with misoprostol, a prostaglandin analog, to bring about an abortion during pregnancy.

An antiprogestogen, that works by blocking the effects of progesterone, making the cervix easier to open, and promoting contraction of the uterus when exposed to misoprostol.

The combination is 97% effective during the first 63 days of pregnancy.

Mifepristone is also effective in the second trimester of pregnancy.

The effectiveness increases to greater than 90% if the misoprostol is given after the mifepristone.

It is taken by mouth.

Pregnancy category US: X (Contraindicated)

Bioavailability 69%.

Protein binding 98%.

Metabolized in the liver.

Excretion in Feces: 83%, Urine: 9%

Common side effects include abdominal pain, feeling tired, and vaginal bleeding.

Serious side effects include: heavy vaginal bleeding, pelvic inflammatory disease bacterial infection, and a malformed baby if the abortive effort is not successful.

Almost all women using the combination of mifepristone/misoprostol regimen experience abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9–16 days.

The most severe cramps after use of misoprostol last for less than 6 hours and can generally be managed with NSAIDs.

Up to 8% of women experienced some type of bleeding for 30 days or more.

Other less common side effects included nausea, vomiting, diarrhea, dizziness, fatigue, and fever.

Serious complications are rare with about 0.04%-0.9% requiring hospitalization and 0.05% requiring blood transfusion.

It is successful and effective at any gestational age.

Mifepristone alone results in abortion within 1–2 weeks in 8% to 46% of pregnancies.

The World Health Organization and the American Congress of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion.

Mifepristone alone is less effective, resulting in abortion within 1–2 weeks in 8% to 46% of pregnancies.

It can also be used for the medical treatment of high blood sugar caused by high cortisol levels in adults with Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.

At low doses has been used for emergency contraception, and to treat symptomatic uterine fibroids.

Use is contraindicated in the presence of adrenal failure, long-term oral corticosteroid therapy, hemorrhagic disorders, inherited porphyria, and hemophilia or anticoagulant use.

It is not effective in treating ectopic pregnancy.

No evidence exists that the effects of mifepristone can be reversed.

In patients with persistent pregnancy after use of mifepristone together with misoprostol for termination, birth defects may occur.

It is steroidal antiprogestogen, an antiglucocorticoid and antiandrogen.

It antagonizes cortisol action competitively at the receptor level.

In the presence of progesterone, it acts as a competitive progesterone receptor antagonist.

In the absence of progesterone, it acts as a partial agonist.

Its relative binding affinity at the progesterone receptor is more than twice that of progesterone.

Its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone, and more than ten times that of cortisol.

Its relative binding affinity at the androgen receptor is less than one-third that of testosterone.

It does not bind to the estrogen receptor or the mineralocorticoid receptor.

At 2 mg daily dose it prevents ovulation.

A single preovulatory 10-mg dose delays ovulation by three to four days and is as effective an emergency contraceptive as a single 1.5-mg dose of the progestin levonorgestrel.

In doses greater or equal to 1 mg/kg it antagonizes the endometrial and myometrial effects of progesterone.

Its antiglucocorticoid effect is manifested at doses greater or equal to 4.5 mg/kg by a compensatory increase in ACTH and cortisol.

Its blockade of progesterone receptors directly causes endometrial decidual degeneration, cervical softening and dilatation, release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins.

It induces decidual breakdown indirectly leads to trophoblast detachment, resulting in decreased syncytiotrophoblast production of hCG, which in turn causes decreased production of progesterone by the corpus luteum.

The elimination half-life is complex.

Metapristone is the major metabolite of mifepristone

Mifepristone was approved for abortion in the United States by the FDA in September 2000.

It is legal and available in all 50 states, Washington, D.C., Guam, and Puerto Rico.

It is a prescription drug, but it is not available to the public through pharmacies.

Its distribution is restricted to specially qualified licensed physicians.

The US Food and Drug Administration approved mifepristone, to end a pregnancy through 70 days gestation (70 days or less since the first day of a woman’s last menstrual period).

It is improved in the United States for use with REMS- risk evaluation and mitigation strategy.

The dosing regimen is 200 mg of mifepristone taken by mouth.

24 to 48 hours after taking mifepristone, 800 mcg of misoprostol is taken buccally.

Mifepristone tablets approved for the treatment of high blood sugar caused by high cortisol levels in the blood in adults with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.

Due to the possibility of adverse reactions such as excessive bleeding, which may require a blood transfusion, and incomplete abortion, which may require surgical intervention, the drug is only considered safe if a physician who is capable of administering a blood transfusion or a surgical abortion is available to the patient in the event of such emergencies.

Mifespristone is a glucocorticoid receptor antagonist approved for the treatment of hyperglycemia associated with Cushing’s disease in patients in whom surgery has failed who are not surgical candidate.

Mifepristone blocks the action of cortisol, corticotropin,and urinary free cortisol levels are increased: adrenal failure, hypokalemia an excessive vaginal bleeding limit its use.