MEDICATIONS: QUESTIONS AND ANSWERS ON MIFEPREX (MIFEPRISTONE)

Mifepristone, also known as RU 486, is a drug that blocks a hormone called progesterone that is needed for pregnancy to continue. Mifepristone, when used together with another medicine called misoprostol, is used to end an early pregnancy (49 days or less since your last menstrual period began).

Yes, mifepristone also has been approved in the United Kingdom, Sweden and other countries.

Some women should not take mifepristone. Do not take mifepristone if it has been more than 49 days since your last menstrual period or if you have:

· An ectopic pregnancy.

· An intrauterine device (IUD) in place (it must be removed before you take mifepristone).

· Problems with your adrenal glands (the glands near your kidneys).

· Been treated with certain steroid medications for a long period of time.

· Bleeding problems or are taking anticoagulant (blood thinning) drug products.

· Had an allergic reaction to mifepristone, misoprostol or similar drugs.

It is important that you understand the need for two follow-up visits with your health care provider and that you have access to a medical care facility in case of an emergency.

Mifepristone has not been studied in women who are heavy smokers. Please tell your doctor if you smoke more than 10 cigarettes a day.

Yes, mifepristone is supplied directly to doctors who meet certain qualifications. It is not available in pharmacies, and it is not legally available over the Internet.

The U.S. Food and Drug Administration’s approval of mifepristone is based on studies of mifepristone that were conducted by doctors who had certain qualifications. Both the drug's sponsor and the 1996 Reproductive Health Drugs Advisory Committee also recommended that the FDA restrict distribution of mifepristone to qualified doctors. FDA has concluded that these restrictions are necessary for the safe use of the drug.

Doctors must have the ability to date pregnancies accurately and to diagnose tubal pregnancies. Doctors also must be qualified to provide any necessary surgery or have made arrangements for any necessary surgery. Doctors must ensure that women have access to medical facilities for emergency care and must agree to other responsibilities, such as dispensing the Medication Guide and reporting any adverse events to the sponsor.

Some states allow physicians to supervise other health care practitioners, such as certified registered nurse practitioners and nurse midwives, and these states may allow a supervised health care provider to dispense mifepristone. Health care providers should check their state law provisions.

State law determines whether there are any restrictions on minors obtaining surgical or medical abortions.

The studies that the FDA evaluated when it approved mifepristone included women ages 18 to 45.

Mifepristone treatment will cause vaginal bleeding. In some cases vaginal bleeding can be very heavy. In a few cases, this bleeding will need to be stopped by a surgical procedure.

Other possible side effects of the treatment include diarrhea, nausea, vomiting, headache, dizziness, back pain and tiredness.

The possible side effects are described in the Medication Guide.

A Medication Guide is a leaflet that contains certain FDA-approved information, written especially for patients.

The FDA determined that a Medication Guide was necessary for women to be able to use Mifeprex effectively and safely. It is important for women to be fully informed about how Mifeprex works and about its risks, as well as the need for follow-up visits with their health care provider, especially on the 14th day after mifepristone is administered. The Medication Guide will help ensure that women follow the directions for use and that they return to their health care provider for follow-up visits.

Before you receive mifepristone, your doctor will provide you with the Medication Guide and ask you to sign a statement (Patient Agreement) that you have decided to end your pregnancy.

You can become pregnant again right after your pregnancy ends. If you do not want to get become pregnant again, start using a birth control method of your choice as soon as your pregnancy ends.

The FDA does not endorse or promote any drug product. The agency evaluates all drug applications submitted by sponsors to determine whether a drug is safe and effective for its proposed indication under the conditions of use in the labeling. This means that the benefits of the drug outweigh its risks. The same standards were applied to the new drug application for mifepristone as are applied to all applications.

Insurance coverage is a decision made by your insurance provider. Please call your insurance company if you have questions about whether your particular insurance provider will cover the cost of mifepristone.

The FDA has received reports of ectopic pregnancy (a pregnancy located outside of the womb, such as in the fallopian tubes), including one case of ectopic pregnancy resulting in death; several cases of severe systemic infection (also called sepsis), including several deaths; and a single case of non-fatal heart attack. At this time, it is unknown whether there is a causal relationship between any of these events and the use of Mifeprex and misoprostol.

In many of these cases, misoprostol was given vaginally, not orally; under the approved regimen, misoprostol is given orally. The FDA has not reviewed data on the safety and effectiveness of vaginal administration of misoprostol.

As with all approved drugs, when the FDA receives new information regarding adverse events, the agency reviews the new information and, as appropriate, provides updates to doctors and their patients so that they have information on how to use the drug safely.

Since the approval of Mifeprex in September 2000, the FDA has been informed of six deaths in the United States due to serious infections following medical abortion with mifepristone and misoprostol that the FDA has concluded may possibly be related to the use of these drugs. These women died from sepsis (serious infection involving the bloodstream). Five cases were found to involve infection with bacteria known as Clostridium sordellii and one case involved infection with Clostridium perfringens. Sepsis is a known risk related to any type of abortion. The symptoms in all of these cases of serious infection were not the usual symptoms of sepsis. We do not know whether using Mifeprex and misoprostol caused these deaths. In all but one case, the misoprostol was used intravaginally.

Clostridium sordellii and Clostridium perfringens are bacteria that are anaerobic (they can live without oxygen) and that in very rare cases can produce toxins that are rapidly fatal. Rare infections with C. sordellii can occur following childbirth (both by vaginal delivery and by caesarian section), as well as following medical abortions. C. sordellii infections also can occur rarely with pelvic, abdominal or bone (orthopedic) surgery and deep skin infections.

It is unclear exactly what factors cause the bacteria to produce the toxins.

All providers of medical abortion and emergency room health care practitioners should investigate the possibility of sepsis in women who are undergoing medical abortion and present with nausea, vomiting, or diarrhea and weakness with or without abdominal pain. These symptoms, even without a fever, may indicate a hidden infection. Strong consideration should be given to obtaining a complete blood count in these patients. Significant leukocytosis with a marked left shift and hemoconcentration may be indicative of sepsis.

The FDA-approved regimen for medical abortion consists of taking 600 mg (three 200 mg tablets) of oral mifepristone on Day One and 400 mcg (two 200 mcg tablets) of oral misoprostol on Day Three. The FDA is aware that medical practitioners may be using modified regimens, including prescribing different doses of mifepristone and misoprostol, dosing misoprostol on a different day, and advising the woman that the oral misoprostol tablets may be inserted into the vagina. While some of the modified regimens have been well described in the literature, the safety and effectiveness of Mifeprex dosing regimens, other than the one approved by the FDA, including use of oral misoprostol intravaginally, has not been established by the FDA.

The FDA has no evidence that vaginal use of misoprostol causes infection. The companies making misoprostol tablets have performed and met the usual quality control tests for marketing misoprostol oral tablets.

For four of the fatal cases of C. sordellii sepsis, the FDA has tested batches of mifepristone and misoprostol and has not found any contamination with the type of bacteria involved.

At this time, the FDA does not have sufficient information to recommend the use of preventive antibiotics for all women undergoing medical abortion. Reports of fatal sepsis in women undergoing medical abortion are very rare (one in 100,000). Preventive antibiotic use carries its own risk of serious adverse events, such as severe or fatal allergic reactions. Also, preventive use of antibiotics can stimulate the growth of “superbugs,” bacteria resistant to everyday antibiotics. While the FDA cannot recommend preventive antibiotics, we advise health care practitioners to be vigilant so that patients suspected of having an infection are immediately given antibiotics that would treat infections with bacteria such as C. sordellii.

The FDA works with the U.S. Centers for Disease Control and Prevention and the manufacturer of Mifeprex to investigate all cases of serious infection that are reported following the use of Mifeprex and misoprostol.

An ectopic pregnancy is any pregnancy that develops outside of the womb. It occurs in 2 percent of all pregnancies. The ectopic pregnancy is usually located in one of the fallopian tubes. As the fetus grows, it damages the tube, causing it to rupture (burst) and bleed. Unless they are discovered and treated early, almost 40 percent of ectopic pregnancies rupture suddenly, causing pain and dangerous bleeding in the abdominal cavity. The other 60 percent usually cause slow bleeding in the abdomen. Ruptured ectopic pregnancies can be fatal. According to data gathered by the CDC from death certificates in the United States, 237 women were reported to have died of ectopic pregnancies between 1991 and 1999.

The Mifeprex labeling states that the use of Mifeprex and misoprostol for the termination of pregnancy is contraindicated in patients with confirmed or suspected ectopic pregnancy. Mifeprex is not an effective treatment for an ectopic pregnancy.

In other countries, in the early 1990s, three prostaglandins — misoprostol, sulprostone and gemeprost — were used with mifepristone to terminate pregnancy. Heart attacks due to coronary spasm, one of them fatal, were reported in three of the more than 60,000 women given sulprostone (an injected prostaglandin) with mifepristone in other countries. As a result, sulprostone is no longer used in combination with mifepristone for medical abortion. Two cases of coronary spasm, one resulting in a heart attack, were reported for gemeprost when used in combination with mifepristone for medical abortion. Neither sulprostone nor gemeprost are approved for use in the United States.

At this time, the FDA believes that the benefits of Mifeprex outweigh the risks. As it does with all prescription drugs, the FDA continues to monitor the safety and effectiveness of mifepristone.