Drug Information Update: Mifeprex Questions and Answers

1. What is MIFEPREX (mifepristone) and how does it work?
Mifepristone 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).

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

3. Who should not take mifepristone?
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 2 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.
For more information please visit: Mifeprex
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111328.htm


Mifeprex Questions and Answers
(Issued 8/29/2007 Updated 2/24/2010)

1. What is MIFEPREX (mifepristone) and how does it work?

Mifepristone 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).

2. Is mifepristone approved in any other countries?

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

3. Who should not take mifepristone?

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 2 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.

4. Is mifepristone distribution restricted?

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.

5. Why are there restrictions for this drug?

FDA'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 FDA restrict distribution of mifepristone to qualified doctors. FDA has concluded that these restrictions are necessary for the safe use of the drug.

6. What qualifications must doctors have to obtain mifepristone?

Doctors must have the ability to date pregnancies accurately and to diagnose tubal pregnancies. Doctors must also 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.

7. Can health care providers other than doctors dispense mifepristone?

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.

8. Is there an age restriction for termination of pregnancy?

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

9. Are there studies with mifepristone in women under the age of 18?

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

10. What are the possible side effects of using mifepristone?

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. Please read the Medication Guide1.

11. What is a Medication Guide?

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

12. Why did FDA develop a Medication Guide for Mifeprex?

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.

13. Can I become pregnant again if I take mifepristone?

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.

14. Does FDA endorse the use of this drug?

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.

15. How much does mifepristone cost?

Manufacturers establish prices for prescription drugs. FDA has no input into or jurisdiction over drug pricing.

16. Will insurance companies pay for mifepristone?

The FDA has no input into or legal control over whether an insurance company does or does not cover the cost of a drug. 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.
17. What serious adverse events have been reported after mifepristone use?

FDA has received reports of ectopic pregnancy (a pregnancylocated 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. FDA has not reviewed data on the safety and effectiveness of vaginal administration of misoprostol.

As with all approved drugs, when 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.

18. What does FDA know about serious infections reported with Mifeprex use?

Since the approval of Mifeprex in September 2000, FDA has been informed of eight deaths in the United States due to serious infections following medical abortion with mifepristone and misoprostol that FDA has concluded may possibly be related to the use of these drugs. These women died from sepsis (serious infection involving the bloodstream). Seven 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.

19. What are Clostridium sordellii and Clostridium perfringens?

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 can also 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.

20. Why are serious infections included in the WARNINGS section of the Mifeprex labeling?

All providers of medical abortion and emergency room healthcare 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.

21. Why are women using misoprostol vaginally?

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. 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 FDA, including use of oral misoprostol intravaginally, has not been established by the FDA.

22. Does the vaginal use of oral misoprostol tablets in medical abortion cause infection?

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, FDA has tested batches of mifepristone and misoprostol and has not found any contamination with the type of bacteria involved.

23. Should women undergoing medical abortion be getting antibiotics to prevent fatal infections?

At this time, 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 (1 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 FDA cannot recommend preventive antibiotics, we advise healthcare 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.

24. What steps are being taken to investigate new cases of serious infection?

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

25. What is a ruptured ectopic pregnancy and how often does this happen?

An ectopic pregnancy is any pregnancy that develops outside of the womb. It occurs in 2% 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% of ectopic pregnancies rupture suddenly, causing pain and dangerous bleeding in the abdominal cavity. The other 60% usually cause slow bleeding in the abdomen. Ruptured ectopic pregnancies can be fatal. According to data gathered by the Centers for Disease Control from death certificates in the U.S., 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.

26. Are there any reports of heart attacks following use of mifepristone with drugs other than misoprostol?

In other countries, in the early 1990’s, 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 U.S.

27. Is FDA considering withdrawing Mifeprex from the market?

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